Targeting natural killer cells and natural killer T cells in cancer (original) (raw)

• Janeway, C. A. Jr & Medzhitov, R. Innate immune recognition. Annu. Rev. Immunol. 20, 197–216 (2002).
  CAS PubMed Google Scholar
• Beutler, B. Innate immunity: an overview. Mol. Immunol. 40, 845–859 (2004).
  Article CAS PubMed Google Scholar
• Akira, S., Takeda, K. & Kaisho, T. Toll-like receptors: critical proteins linking innate and acquired immunity. Nature Immunol. 2, 675–680 (2001).
  Article CAS Google Scholar
• Spits, H. & Di Santo, J. P. The expanding family of innate lymphoid cells: regulators and effectors of immunity and tissue remodeling. Nature Immunol. 12, 21–27 (2011).
  Article CAS Google Scholar
• Vivier, E. et al. Innate or adaptive immunity? The example of natural killer cells. Science 331, 44–49 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Oldham, R. K. & Herberman, R. B. Evaluation of cell-mediated cytotoxic reactivity against tumor associated antigens with 125I-iododeoxyuridine labeled target cells. J. Immunol. 111, 862–871 (1973).
  CAS PubMed Google Scholar
• Herberman, R. B., Nunn, M. E. & Lavrin, D. H. Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic acid allogeneic tumors. I. Distribution of reactivity and specificity. Int. J. Cancer 16, 216–229 (1975).
  Article CAS PubMed Google Scholar
• Kiessling, R., Klein, E. & Wigzell, H. “Natural” killer cells in the mouse. I. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Specificity and distribution according to genotype. Eur. J. Immunol. 5, 112–117 (1975).
  Article CAS PubMed Google Scholar
• Smyth, M. J., Hayakawa, Y., Takeda, K. & Yagita, H. New aspects of natural-killer-cell surveillance and therapy of cancer. Nature Rev. Cancer 2, 850–861 (2002).
  Article CAS Google Scholar
• Vesely, M. D., Kershaw, M. H., Schreiber, R. D. & Smyth, M. J. Natural innate and adaptive immunity to cancer. Annu. Rev. Immunol. 29, 235–271 (2011).
  Article CAS PubMed Google Scholar
• Orange, J. S. & Ballas, Z. K. Natural killer cells in human health and disease. Clin. Immunol. 118, 1–10 (2006).
  Article CAS PubMed Google Scholar
• Imai, K., Matsuyama, S., Miyake, S., Suga, K. & Nakachi, K. Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet 356, 1795–1799 (2000). One of the very few epidemiological studies to suggest a role for NK cells in the control of tumours in humans.
  Article CAS PubMed Google Scholar
• Carrega, P. et al. Natural killer cells infiltrating human nonsmall-cell lung cancer are enriched in CD56brightCD16− cells and display an impaired capability to kill tumor cells. Cancer 112, 863–875 (2008).
  Article PubMed Google Scholar
• Platonova, S. et al. Profound coordinated alterations of intratumoral NK cell phenotype and function in lung carcinoma. Cancer Res. 71, 5412–5422 (2011).
  Article CAS PubMed Google Scholar
• Eckl, J. et al. Transcript signature predicts tissue NK cell content and defines renal cell carcinoma subgroups independent of TNM staging. J. Mol. Med. 90, 55–66 (2011).
  Article CAS PubMed Google Scholar
• Halama, N. et al. Natural killer cells are scarce in colorectal carcinoma tissue despite high levels of chemokines and cytokines. Clin. Cancer Res. 17, 678–689 (2011).
  Article CAS PubMed Google Scholar
• Menard, C. et al. Natural killer cell IFN-γ levels predict long-term survival with imatinib mesylate therapy in gastrointestinal stromal tumor-bearing patients. Cancer Res. 69, 3563–3569 (2009).
  Article CAS PubMed Google Scholar
• Kronenberg, M. & Gapin, L. The unconventional lifestyle of NKT cells. Nature Rev. Immunol. 2, 557–568 (2002).
  Article CAS Google Scholar
• Tilloy, F. et al. An invariant T cell receptor α chain defines a novel TAP-independent major histocompatibility complex class Ib-restricted α/β T cell subpopulation in mammals. J. Exp. Med. 189, 1907–1921 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Benlagha, K., Kyin, T., Beavis, A., Teyton, L. & Bendelac, A. A thymic precursor to the NK T cell lineage. Science 296, 553–555 (2002).
  Article CAS PubMed Google Scholar
• Gapin, L., Matsuda, J. L., Surh, C. D. & Kronenberg, M. NKT cells derive from double-positive thymocytes that are positively selected by CD1d. Nature Immunol. 2, 971–978 (2001).
  Article CAS Google Scholar
• Egawa, T. et al. Genetic evidence supporting selection of the Vα14i NKT cell lineage from double-positive thymocyte precursors. Immunity 22, 705–716 (2005).
  Article CAS PubMed Google Scholar
• Lantz, O. & Bendelac, A. An invariant T cell receptor α chain is used by a unique subset of major histocompatibility complex class I-specific CD4+ and CD4−8− T cells in mice and humans. J. Exp. Med. 180, 1097–1106 (1994).
  Article CAS PubMed Google Scholar
• Porcelli, S., Yockey, C. E., Brenner, M. B. & Balk, S. P. Analysis of T cell antigen receptor (TCR) expression by human peripheral blood CD4−8− α/β T cells demonstrates preferential use of several Vβ genes and an invariant TCR α chain. J. Exp. Med. 178, 1–16 (1993).
  Article CAS PubMed Google Scholar
• Schumann, J., Voyle, R. B., Wei, B. Y. & MacDonald, H. R. Cutting edge: influence of the TCR Vβ domain on the avidity of CD1d:α-galactosylceramide binding by invariant Vα14 NKT cells. J. Immunol. 170, 5815–5819 (2003).
  Article PubMed Google Scholar
• Wei, D. G., Curran, S. A., Savage, P. B., Teyton, L. & Bendelac, A. Mechanisms imposing the Vβ bias of Vα14 natural killer T cells and consequences for microbial glycolipid recognition. J. Exp. Med. 203, 1197–1207 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Zhou, D. et al. Lysosomal glycosphingolipid recognition by NKT cells. Science 306, 1786–1789 (2004).
  CAS PubMed Google Scholar
• Pei, B. et al. Diverse endogenous antigens for mouse NKT cells: self-antigens that are not glycosphingolipids. J. Immunol. 186, 1348–1360 (2011). This study suggests that the self antigens recognized by NKT cells may not be exclusively glycosphingolipids.
  Article CAS PubMed Google Scholar
• Venkataswamy, M. M. & Porcelli, S. A. Lipid and glycolipid antigens of CD1d-restricted natural killer T cells. Semin. Immunol. 22, 68–78 (2010).
  Article CAS PubMed Google Scholar
• Brigl, M. & Brenner, M. B. CD1: antigen presentation and T cell function. Annu. Rev. Immunol. 22, 817–890 (2004).
  Article CAS PubMed Google Scholar
• Kronenberg, M. Toward an understanding of NKT cell biology: progress and paradoxes. Annu. Rev. Immunol. 23, 877–900 (2004).
  Article CAS Google Scholar
• Godfrey, D. I., Pellicci, D. G. & Smyth, M. J. Immunology: the elusive NKT cell antigen — is the search over? Science 306, 1687–1689 (2004).
  Article CAS PubMed Google Scholar
• Bendelac, A., Savage, P. B. & Teyton, L. The biology of NKT cells. Annu. Rev. Immunol. 25, 297–336 (2006).
  Article CAS Google Scholar
• Smyth, M. J. et al. Differential tumor surveillance by natural killer (NK) and NKT cells. J. Exp. Med. 191, 661–668 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Swann, J. B. et al. Type I natural killer T cells suppress tumors caused by p53 loss in mice. Blood 113, 6382–6385 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Nowak, M. et al. Defective NKT cell activation by CD1d+ TRAMP prostate tumor cells is corrected by interleukin-12 with α-galactosylceramide. PLoS ONE 5, e11311 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Bellone, M. et al. iNKT cells control mouse spontaneous carcinoma independently of tumor-specific cytotoxic T cells. PLoS ONE 5, e8646 (2010). References 34–37 suggest a tumour immunosurveillance role for NKT cells.
  Article CAS PubMed PubMed Central Google Scholar
• Savage, A. K. et al. The transcription factor PLZF directs the effector program of the NKT cell lineage. Immunity 29, 391–403 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Kovalovsky, D. et al. The BTB–zinc finger transcriptional regulator PLZF controls the development of invariant natural killer T cell effector functions. Nature Immunol. 9, 1055–1064 (2008).
  Article CAS Google Scholar
• Gascoyne, D. M. et al. The basic leucine zipper transcription factor E4BP4 is essential for natural killer cell development. Nature Immunol. 10, 1118–1124 (2009).
  Article CAS Google Scholar
• Kamizono, S. et al. Nfil3/E4bp4 is required for the development and maturation of NK cells in vivo. J. Exp. Med. 206, 2977–2986 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Sun, J. C., Beilke, J. N. & Lanier, L. L. Adaptive immune features of natural killer cells. Nature 457, 557–561 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Wesley, J. D., Tessmer, M. S., Chaukos, D. & Brossay, L. NK cell-like behavior of Vα14i NK T cells during MCMV infection. PLoS Pathog. 4, e1000106 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Tyznik, A. J. et al. Cutting edge: the mechanism of invariant NKT cell responses to viral danger signals. J. Immunol. 181, 4452–4456 (2008).
  Article CAS PubMed Google Scholar
• Brigl, M. et al. Innate and cytokine-driven signals, rather than microbial antigens, dominate in natural killer T cell activation during microbial infection. J. Exp. Med. 208, 1163–1177 (2011). References 43–45 suggest that NKT cells can behave as innate immune cells.
  Article CAS PubMed PubMed Central Google Scholar
• Stetson, D. B. et al. Constitutive cytokine mRNAs mark natural killer (NK) and NK T cells poised for rapid effector function. J. Exp. Med. 198, 1069–1076 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Matsuda, J. L. et al. Homeostasis of Vα14i NKT cells. Nature Immunol. 3, 966–974 (2002).
  Article CAS Google Scholar
• Ranson, T. et al. IL-15 availability conditions homeostasis of peripheral natural killer T cells. Proc. Natl Acad. Sci. USA 100, 2663–2668 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Townsend, M. J. et al. T-bet regulates the terminal maturation and homeostasis of NK and Vα14i NKT cells. Immunity 20, 477–494 (2004).
  Article CAS PubMed Google Scholar
• Wingender, G., Krebs, P., Beutler, B. & Kronenberg, M. Antigen-specific cytotoxicity by invariant NKT cells in vivo is CD95/CD178-dependent and is correlated with antigenic potency. J. Immunol. 185, 2721–2729 (2010).
  Article CAS PubMed Google Scholar
• Carlyle, J. R. et al. Evolution of the Ly49 and Nkrp1 recognition systems. Semin. Immunol. 20, 321–330 (2008).
  Article CAS PubMed Google Scholar
• Parham, P. MHC class I molecules and KIRs in human history, health and survival. Nature Rev. Immunol. 5, 201–214 (2005).
  Article CAS Google Scholar
• Kim, S. et al. Licensing of natural killer cells by host major histocompatibility complex class I molecules. Nature 436, 709–713 (2005).
  Article CAS PubMed Google Scholar
• Fernandez, N. C. et al. A subset of natural killer cells achieves self-tolerance without expressing inhibitory receptors specific for self-MHC molecules. Blood 105, 4416–4423 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Anfossi, N. et al. Human NK cell education by inhibitory receptors for MHC class I. Immunity 25, 331–342 (2006). References 53–55 indicate that MHC class I recognition by NK cell inhibitory receptors contributes to the acquisition of NK cell functions.
  Article CAS PubMed Google Scholar
• Yokoyama, W. M. & Kim, S. How do natural killer cells find self to achieve tolerance? Immunity 24, 249–257 (2006).
  Article CAS PubMed Google Scholar
• Raulet, D. H. & Vance, R. E. Self-tolerance of natural killer cells. Nature Rev. Immunol. 6, 520–531 (2006).
  Article CAS Google Scholar
• Brodin, P., Karre, K. & Hoglund, P. NK cell education: not an on-off switch but a tunable rheostat. Trends Immunol. 30, 143–149 (2009).
  Article CAS PubMed Google Scholar
• Orr, M. T. & Lanier, L. L. Natural killer cell education and tolerance. Cell 142, 847–856 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Hoglund, P. et al. Recognition of β2-microglobulin-negative (β2m−) T-cell blasts by natural killer cells from normal but not from β2m− mice: nonresponsiveness controlled by β2m− bone marrow in chimeric mice. Proc. Natl Acad. Sci. USA 88, 10332–10336 (1991).
  Article CAS PubMed PubMed Central Google Scholar
• Liao, N.-S., Bix, M., Zilstra, M., Jaenish, R. & Raulet, D. MHC class I deficiency: susceptibility to natural killer (NK) cells and impaired NK activity. Science 253, 199–202 (1991).
  Article CAS PubMed Google Scholar
• Orr, M. T., Murphy, W. J. & Lanier, L. L. 'Unlicensed' natural killer cells dominate the response to cytomegalovirus infection. Nature Immunol. 11, 321–327 (2010).
  Article CAS Google Scholar
• Joncker, N. T., Fernandez, N. C., Treiner, E., Vivier, E. & Raulet, D. H. NK cell responsiveness is tuned commensurate with the number of inhibitory receptors for self-MHC class I: the rheostat model. J. Immunol. 182, 4572–4580 (2009).
  Article CAS PubMed Google Scholar
• Brodin, P., Lakshmikanth, T., Johansson, S., Karre, K. & Hoglund, P. The strength of inhibitory input during education quantitatively tunes the functional responsiveness of individual natural killer cells. Blood 113, 2434–2441 (2009).
  Article CAS PubMed Google Scholar
• Guia, S. et al. Confinement of activating receptors at the plasma membrane controls natural killer cell tolerance. Sci. Signal. 4, ra21 (2011).
  Article CAS PubMed Google Scholar
• Joncker, N. T., Shifrin, N., Delebecque, F. & Raulet, D. H. Mature natural killer cells reset their responsiveness when exposed to an altered MHC environment. J. Exp. Med. 207, 2065–2072 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Elliott, J. M., Wahle, J. A. & Yokoyama, W. M. MHC class I-deficient natural killer cells acquire a licensed phenotype after transfer into an MHC class I-sufficient environment. J. Exp. Med. 207, 2073–2079 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Kijima, M., Gardiol, N. & Held, W. Natural killer cell mediated missing-self recognition can protect mice from primary chronic myeloid leukemia in vivo. PLoS ONE 6, e27639 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Bottino, C., Moretta, L. & Moretta, A. NK cell activating receptors and tumor recognition in humans. Curr. Top. Microbiol. Immunol. 298, 175–182 (2006).
  CAS PubMed Google Scholar
• Moretta, A. et al. Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu. Rev. Immunol. 19, 197–223 (2001). This review covers the discovery of activating NK cell receptors.
  Article CAS PubMed Google Scholar
• Bauer, S. et al. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science 285, 727–729 (1999).
  Article CAS PubMed Google Scholar
• Raulet, D. H. & Guerra, N. Oncogenic stress sensed by the immune system: role of natural killer cell receptors. Nature Rev. Immunol. 9, 568–580 (2009).
  Article CAS Google Scholar
• Raulet, D. H. Roles of the NKG2D immunoreceptor and its ligands. Nature Rev. Immunol. 3, 781–790 (2003).
  Article CAS Google Scholar
• Diefenbach, A., Jamieson, A. M., Liu, S. D., Shastri, N. & Raulet, D. H. Ligands for the murine NKG2D receptor: expression by tumor cells and activation of NK cells and macrophages. Nature Immunol. 1, 119–126 (2000).
  Article CAS Google Scholar
• Cerwenka, A. et al. Retinoic acid early inducible genes define a ligand family for the activating NKG2D receptor in mice. Immunity 12, 721–727 (2000).
  Article CAS PubMed Google Scholar
• Cosman, D. et al. ULBPs, novel MHC class I-related molecules, bind to CMV glycoprotein UL16 and stimulate NK cytotoxicity through the NKG2D receptor. Immunity 14, 123–133 (2001).
  Article CAS PubMed Google Scholar
• Carayannopoulos, L. N. et al. Ligands for murine NKG2D display heterogenous binding behavior. Eur. J. Immunol. 32, 597–605 (2002). References 74–77 report the identification of NKG2D ligands.
  Article CAS PubMed Google Scholar
• Guerra, N. et al. NKG2D-deficient mice are defective in tumor surveillance in models of spontaneous malignancy. Immunity 28, 571–580 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Unni, A. M., Bondar, T. & Medzhitov, R. Intrinsic sensor of oncogenic transformation induces a signal for innate immunosurveillance. Proc. Natl Acad. Sci. USA 105, 1686–1691 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Gasser, S., Orsulic, S., Brown, E. J. & Raulet, D. H. The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature 436, 1186–1190 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Soriani, A. et al. ATM-ATR dependent up-regulation of DNAM-1 and NKG2D ligands on multiple myeloma cells by therapeutic agents results in enhanced NK cell susceptibility and is associated with a senescent phenotype. Blood 113, 3503–3511 (2008).
  Article CAS PubMed Google Scholar
• Sivori, S. et al. p46, a novel natural killer cell-specific surface molecule that mediates cell activation. J. Exp. Med. 186, 1129–1136 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Vitale, M. et al. NKp44, a novel triggering surface molecule specifically expressed by activated natural killer cells, is involved in non-major histocompatibility complex-restricted tumor cell lysis. J. Exp. Med. 187, 2065–2072 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Pende, D. et al. Identification and molecular characterization of NKp30, a novel triggering receptor involved in natural cytotoxicity mediated by human natural killer cells. J. Exp. Med. 190, 1505–1516 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Brandt, C. S. et al. The B7 family member B7-H6 is a tumor cell ligand for the activating natural killer cell receptor NKp30 in humans. J. Exp. Med. 206, 1495–1503 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Li, Y., Wang, Q. & Mariuzza, R. A. Structure of the human activating natural cytotoxicity receptor NKp30 bound to its tumor cell ligand B7-H6. J. Exp. Med. 208, 703–714 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Bottino, C. et al. Identification of PVR (CD155) and Nectin-2 (CD112) as cell surface ligands for the human DNAM-1 (CD226) activating molecule. J. Exp. Med. 198, 557–567 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Cartron, G. et al. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcγRIIIa gene. Blood 99, 754–758 (2002). This study reveals the importance of CD16 for monoclonal antibody therapies in humans.
  Article CAS PubMed Google Scholar
• Veeramani, S. et al. Rituximab infusion induces NK activation in lymphoma patients with the high-affinity CD16 polymorphism. Blood 118, 3347–3349 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Terme, M., Ullrich, E., Delahaye, N. F., Chaput, N. & Zitvogel, L. Natural killer cell-directed therapies: moving from unexpected results to successful strategies. Nature Immunol. 9, 486–494 (2008).
  Article CAS Google Scholar
• Thomas, E. et al. Bone marrow transplantation. N. Engl. J. Med. 292, 832–843; 895–902 (1975).
  Article CAS PubMed Google Scholar
• Weiden, P. L. et al. Antileukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts. N. Engl. J. Med. 300, 1068–1073 (1979).
  Article CAS PubMed Google Scholar
• Storb, R. Allogeneic hematopoietic stem cell transplantation — yesterday, today, and tomorrow. Exp. Hematol. 31, 1–10 (2003).
  Article PubMed Google Scholar
• Childs, R. et al. Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. N. Engl. J. Med. 343, 750–758 (2000).
  Article CAS PubMed Google Scholar
• Blaise, D. et al. Reduced-intensity preparative regimen and allogeneic stem cell transplantation for advanced solid tumors. Blood 103, 435–441 (2004).
  Article CAS PubMed Google Scholar
• Ferrara, J. L., Levine, J. E., Reddy, P. & Holler, E. Graft-versus-host disease. Lancet 373, 1550–1561 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Dong, Z. et al. Essential function for SAP family adaptors in the surveillance of hematopoietic cells by natural killer cells. Nature Immunol. 10, 973–980 (2009).
  Article CAS Google Scholar
• Aversa, F. et al. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N. Engl. J. Med. 339, 1186–1193 (1998).
  Article CAS PubMed Google Scholar
• Ruggeri, L. et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 295, 2097–2100 (2002). A demonstration of the clinical antitumour activity of human NK cells, in the peculiar context of haplotype-mismatched, allogeneic T cell-depleted haematopoietic stem cell transplantation following administration of a myeloablative conditioning regimen.
  Article CAS PubMed Google Scholar
• Giebel, S. et al. Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors. Blood 102, 814–819 (2003).
  Article CAS PubMed Google Scholar
• Ruggeri, L. et al. Donor natural killer cell allorecognition of missing self in haploidentical hematopoietic transplantation for acute myeloid leukemia: challenging its predictive value. Blood 110, 433–440 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Kroger, N. et al. Comparison between antithymocyte globulin and alemtuzumab and the possible impact of KIR-ligand mismatch after dose-reduced conditioning and unrelated stem cell transplantation in patients with multiple myeloma. Br. J. Haematol. 129, 631–643 (2005).
  Article CAS PubMed Google Scholar
• Bignon, J. D. & Gagne, K. KIR matching in hematopoietic stem cell transplantation. Curr. Opin. Immunol. 17, 553–559 (2005).
  Article CAS PubMed Google Scholar
• Poggi, A. & Zocchi, M. R. Cyclosporin A regulates human NK cell apoptosis induced by soluble HLA-I or by target cells. Autoimmun. Rev. 4, 532–536 (2005).
  Article CAS PubMed Google Scholar
• Wang, H. et al. The unexpected effect of cyclosporin A on CD56+CD16− and CD56+CD16+ natural killer cell subpopulations. Blood 110, 1530–1539 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Moretta, A. et al. Existence of both inhibitory (p58) and activatory (p50) receptors for HLA-C molecules in human natural killer cells. J. Exp. Med. 182, 875–884 (1995).
  Article CAS PubMed Google Scholar
• Olcese, L. et al. Killer-cell activatory receptors for MHC class I molecules are included in a multimeric complex expressed by human killer cells. J. Immunol. 158, 5083–5086 (1997).
  CAS PubMed Google Scholar
• Lanier, L. L., Corliss, B. C., Wu, J., Leong, C. & Phillips, J. H. Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells. Nature 391, 703–707 (1998).
  Article CAS PubMed Google Scholar
• Verheyden, S., Schots, R., Duquet, W. & Demanet, C. A defined donor activating natural killer cell receptor genotype protects against leukemic relapse after related HLA-identical hematopoietic stem cell transplantation. Leukemia 19, 1446–1451 (2005).
  Article CAS PubMed Google Scholar
• De Santis, D. et al. Natural killer cell HLA-C epitopes and killer cell immunoglobulin-like receptors both influence outcome of mismatched unrelated donor bone marrow transplants. Tissue Antigens 65, 519–528 (2005).
  Article CAS PubMed Google Scholar
• Cook, M. et al. Donor KIR genotype has a major influence on the rate of cytomegalovirus reactivation following T-cell replete stem cell transplantation. Blood 107, 1230–1232 (2006).
  Article CAS PubMed Google Scholar
• Chen, C. et al. Activating KIR genes are associated with CMV reactivation and survival after non-T-cell depleted HLA-identical sibling bone marrow transplantation for malignant disorders. Bone Marrow Transplant. 38, 437–444 (2006).
  Article CAS PubMed Google Scholar
• McQueen, K. L. et al. Donor–recipient combinations of group A and B KIR haplotypes and HLA class I ligand affect the outcome of HLA-matched, sibling donor hematopoietic cell transplantation. Hum. Immunol. 68, 309–323 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Clausen, J. et al. Impact of natural killer cell dose and donor killer-cell immunoglobulin-like receptor (KIR) genotype on outcome following human leucocyte antigen-identical haematopoietic stem cell transplantation. Clin. Exp. Immunol. 148, 520–528 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Holler, E. et al. Increased serum levels of tumor necrosis factor α precede major complications of bone marrow transplantation. Blood 75, 1011–1016 (1990).
  CAS PubMed Google Scholar
• Storb, R. et al. Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation. Blood 89, 3048–3054 (1997).
  CAS PubMed Google Scholar
• Giralt, S. et al. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood 89, 4531–4536 (1997).
  CAS PubMed Google Scholar
• Slavin, S. et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood 91, 756–763 (1998).
  CAS PubMed Google Scholar
• Blaise, D., Vey, N., Faucher, C. & Mohty, M. Current status of reduced-intensity-conditioning allogeneic stem cell transplantation for acute myeloid leukemia. Haematologica 92, 533–541 (2007).
  Article PubMed Google Scholar
• Gratwohl, A. et al. The EBMT activity survey 2007 with focus on allogeneic HSCT for AML and novel cellular therapies. Bone Marrow Transplant. 43, 275–291 (2009).
  Article CAS PubMed Google Scholar
• Pende, D. et al. Anti-leukemia activity of alloreactive NK cells in KIR ligand-mismatched haploidentical HSCT for pediatric patients: evaluation of the functional role of activating KIR and redefinition of inhibitory KIR specificity. Blood 113, 3119–3129 (2009).
  Article CAS PubMed Google Scholar
• Mohty, M. et al. Recovery of lymphocyte and dendritic cell subsets following reduced intensity allogeneic bone marrow transplantation. Hematology 7, 157–164 (2002).
  Article CAS PubMed Google Scholar
• Larosa, F. et al. Peripheral T-cell expansion and low infection rate after reduced-intensity conditioning and allogeneic blood stem cell transplantation. Bone Marrow Transplant. 35, 859–868 (2005).
  Article CAS PubMed Google Scholar
• Kim, D. H. et al. Non-CD34+ cells, especially CD8+ cytotoxic T cells and CD56+ natural killer cells, rather than CD34 cells, predict early engraftment and better transplantation outcomes in patients with hematologic malignancies after allogeneic peripheral stem cell transplantation. Biol. Blood Marrow Transplant. 12, 719–728 (2006).
  Article CAS PubMed Google Scholar
• Savani, B. N. et al. Rapid natural killer cell recovery determines outcome after T-cell-depleted HLA-identical stem cell transplantation in patients with myeloid leukemias but not with acute lymphoblastic leukemia. Leukemia 21, 2145–2152 (2007).
  Article CAS PubMed Google Scholar
• Dunbar, E. M. et al. The relationship between circulating natural killer cells after reduced intensity conditioning hematopoietic stem cell transplantation and relapse-free survival and graft-versus-host disease. Haematologica 93, 1852–1858 (2008).
  Article PubMed Google Scholar
• Kolb, H. J. et al. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. Blood 86, 2041–2050 (1995).
  CAS PubMed Google Scholar
• Dazzi, F. et al. Durability of responses following donor lymphocyte infusions for patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia. Blood 96, 2712–2716 (2000).
  CAS PubMed Google Scholar
• Marks, D. I. et al. The toxicity and efficacy of donor lymphocyte infusions given after reduced-intensity conditioning allogeneic stem cell transplantation. Blood 100, 3108–3114 (2002).
  Article CAS PubMed Google Scholar
• Shimoni, A. et al. Long-term follow-up of recipients of CD8-depleted donor lymphocyte infusions for the treatment of chronic myelogenous leukemia relapsing after allogeneic progenitor cell transplantation. Biol. Blood Marrow Transplant. 7, 568–575 (2001).
  Article CAS PubMed Google Scholar
• Alyea, E. P. et al. CD8+ cell depletion of donor lymphocyte infusions using CD8 monoclonal antibody-coated high-density microparticles (CD8-HDM) after allogeneic hematopoietic stem cell transplantation: a pilot study. Bone Marrow Transplant. 34, 123–128 (2004).
  Article CAS PubMed Google Scholar
• Porter, D. L. et al. Graft-versus-tumor induction with donor leukocyte infusions as primary therapy for patients with malignancies. J. Clin. Oncol. 17, 1234 (1999).
  Article CAS PubMed Google Scholar
• Guo, M. et al. Infusion of HLA-mismatched peripheral blood stem cells improves the outcome of chemotherapy for acute myeloid leukemia in elderly patients. Blood 117, 936–941 (2011).
  Article CAS PubMed Google Scholar
• Miller, J. S. et al. Large scale ex vivo expansion and activation of human natural killer cells for autologous therapy. Bone Marrow Transplant. 14, 555–562 (1994).
  CAS PubMed Google Scholar
• Passweg, J. R. et al. Purified donor NK-lymphocyte infusion to consolidate engraftment after haploidentical stem cell transplantation. Leukemia 18, 1835–1838 (2004).
  Article CAS PubMed Google Scholar
• McKenna, D. H. Jr. et al. Good manufacturing practices production of natural killer cells for immunotherapy: a six-year single-institution experience. Transfusion 47, 520–528 (2007).
  Article CAS PubMed Google Scholar
• Lundqvist, A., McCoy, J. P., Samsel, L. & Childs, R. Reduction of GVHD and enhanced antitumor effects after adoptive infusion of alloreactive Ly49-mismatched NK cells from MHC-matched donors. Blood 109, 3603–3606 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Castriconi, R. et al. Human NK cell infusions prolong survival of metastatic human neuroblastoma-bearing NOD/scid mice. Cancer Immunol. Immunother. 56, 1733–1742 (2007).
  Article CAS PubMed Google Scholar
• Shi, J. et al. Infusion of haplo-identical killer immunoglobulin-like receptor ligand mismatched NK cells for relapsed myeloma in the setting of autologous stem cell transplantation. Br. J. Haematol. 143, 641–653 (2008).
  Article PubMed PubMed Central Google Scholar
• Arai, S. et al. Infusion of the allogeneic cell line NK-92 in patients with advanced renal cell cancer or melanoma: a phase I trial. Cytotherapy 10, 625–632 (2008).
  Article CAS PubMed Google Scholar
• Cho, D. & Campana, D. Expansion and activation of natural killer cells for cancer immunotherapy. Korean J. Lab. Med. 29, 89–96 (2009).
  Article CAS PubMed Google Scholar
• Barkholt, L. et al. Safety analysis of _ex vivo_-expanded NK and NK-like T cells administered to cancer patients: a phase I clinical study. Immunotherapy 1, 753–764 (2009).
  Article CAS PubMed Google Scholar
• Bachanova, V. et al. Allogeneic natural killer cells for refractory lymphoma. Cancer Immunol. Immunother. 59, 1739–1744 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Nguyen, S. et al. Infusion of allogeneic natural killer cells in a patient with acute myeloid leukemia in relapse after haploidentical hematopoietic stem cell transplantation. Transfusion 51, 1769–1778 (2011).
  Article PubMed Google Scholar
• Geller, M. A. et al. A phase II study of allogeneic natural killer cell therapy to treat patients with recurrent ovarian and breast cancer. Cytotherapy 13, 98–107 (2011).
  Article CAS PubMed Google Scholar
• De Somer, L. et al. Recipient lymphocyte infusion in MHC-matched bone marrow chimeras induces a limited lymphohematopoietic host-versus-graft reactivity but a significant antileukemic effect mediated by CD8+ T cells and natural killer cells. Haematologica 96, 424–431 (2011).
  Article CAS PubMed Google Scholar
• Curti, A. et al. Successful transfer of alloreactive haploidentical KIR ligand-mismatched natural killer cells after infusion in elderly high risk acute myeloid leukemia patients. Blood 118, 3273–3279 (2011).
  Article CAS PubMed Google Scholar
• Brehm, C. et al. IL-2 stimulated but not unstimulated NK cells induce selective disappearance of peripheral blood cells: concomitant results to a phase I/II study. PLoS ONE 6, e27351 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Miller, J. S. et al. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood 105, 3051–3057 (2005). A demonstration of the safety and potential efficacy of NK cell infusion as a cancer therapy in humans.
  Article CAS PubMed Google Scholar
• Alici, E. IPH-2101, a fully human anti-NK-cell inhibitory receptor mAb for the potential treatment of hematological cancers. Curr. Opin. Mol. Ther. 12, 724–733 (2010).
  CAS PubMed Google Scholar
• Romagne, F. et al. Pre-clinical characterization of 1–7F9, a novel human anti-KIR therapeutic antibody that augments NK-mediated killing of tumor cells. Blood 114, 2667–2677 (2009). A characterization of the first KIR-specific human monoclonal antibody.
  Article CAS PubMed PubMed Central Google Scholar
• Romagne, F. & Vivier, E. Natural killer cell-based therapies. F1000 Med. Rep. 3, 9 (2011).
  Article PubMed PubMed Central Google Scholar
• Sola, C. et al. Genetic and antibody-mediated reprogramming of natural killer cell missing-self recognition in vivo. Proc. Natl Acad. Sci. USA 106, 12879–12884 (2009). This paper describes preclinical models of the safety and efficacy of targeting MHC class I-specific inhibitory receptors using monoclonal antibodies.
  Article CAS PubMed PubMed Central Google Scholar
• Benson, D. M. et al. A phase I study of IPH2101, a novel anti-inhibitory KIR monoclonal antibody, in patients with multiple myeloma. J. Clin. Oncol. 28 (15 suppl.), 8139 (2010).
  Article Google Scholar
• Vey, N. et al. A phase I study of the anti-natural killer inhibitory receptor (KIR) monoclonal antibody (1–7F9, IPH2101) in elderly patients with acute myeloid leukemia (AML). J. Clin. Oncol. 27 (15 suppl.), 3015 (2009).
  Google Scholar
• Benson, D. M. Jr. et al. IPH2101, a novel anti-inhibitory KIR antibody, and lenalidomide combine to enhance the natural killer cell versus multiple myeloma effect. Blood 118, 6387–6391 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Walzer, T. & Vivier, E. G-protein-coupled receptors in control of natural killer cell migration. Trends Immunol. 32, 486–492 (2011).
  Article CAS PubMed Google Scholar
• Brand, J. M. et al. Kinetics and organ distribution of allogeneic natural killer lymphocytes transfused into patients suffering from renal cell carcinoma. Stem Cells Dev. 13, 307–314 (2004).
  Article CAS PubMed Google Scholar
• Sun, J. C. & Lanier, L. L. NK cell development, homeostasis and function: parallels with CD8 T cells. Nature Rev. Immunol. 11, 645–657 (2011).
  Article CAS Google Scholar
• Park, S. H., Kyin, T., Bendelac, A. & Carnaud, C. The contribution of NKT cells, NK cells, and other γ-chain-dependent non-T non-B cells to IL-12-mediated rejection of tumors. J. Immunol. 170, 1197–1201 (2003).
  Article CAS PubMed Google Scholar
• Smyth, M. J. et al. Sequential production of interferon-γ by NK1.1+ T cells and natural killer cells is essential for the antimetastatic effect of α-galactosylceramide. Blood 99, 1259–1266 (2002).
  Article CAS PubMed Google Scholar
• Metelitsa, L. S., Weinberg, K. I., Emanuel, P. D. & Seeger, R. C. Expression of CD1d by myelomonocytic leukemias provides a target for cytotoxic NKT cells. Leukemia 17, 1068–1077 (2003).
  Article CAS PubMed Google Scholar
• Renukaradhya, G. J. et al. Type I NKT cells protect (and type II NKT cells suppress) the host's innate antitumor immune response to a B-cell lymphoma. Blood 111, 5637–5645 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Wu, D. Y., Segal, N. H., Sidobre, S., Kronenberg, M. & Chapman, P. B. Cross-presentation of disialoganglioside GD3 to natural killer T cells. J. Exp. Med. 198, 173–181 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Shimizu, K., Kurosawa, Y., Taniguchi, M., Steinman, R. M. & Fujii, S. Cross-presentation of glycolipid from tumor cells loaded with α-galactosylceramide leads to potent and long-lived T cell mediated immunity via dendritic cells. J. Exp. Med. 204, 2641–2653 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Swann, J. B., Coquet, J. M., Smyth, M. J. & Godfrey, D. I. CD1-restricted T cells and tumor immunity. Curr. Top. Microbiol. Immunol. 314, 293–323 (2007).
  CAS PubMed Google Scholar
• Crowe, N. Y., Smyth, M. J. & Godfrey, D. I. A critical role for natural killer T cells in immunosurveillance of methylcholanthrene-induced sarcomas. J. Exp. Med. 196, 119–127 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Kammertoens, T., Qin, Z., Briesemeister, D., Bendelac, A. & Blankenstein, T. B-cells and IL-4 promote methylcholanthrene-induced carcinogenesis but there is no evidence for a role of T/NKT-cells and their effector molecules (Fas-ligand, TNF-α, perforin). Int. J. Cancer 31 Jan 2012 (doi:10.1002/ijc.27411).
  Article CAS PubMed Google Scholar
• Song, L. et al. Vα24-invariant NKT cells mediate antitumor activity via killing of tumor-associated macrophages. J. Clin. Invest. 119, 1524–1536 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Tahir, S. M. et al. Loss of IFN-γ production by invariant NK T cells in advanced cancer. J. Immunol. 167, 4046–4050 (2001).
  Article CAS PubMed Google Scholar
• Yanagisawa, K. et al. Impaired proliferative response of Vα24 NKT cells from cancer patients against α-galactosylceramide. J. Immunol. 168, 6494–6499 (2002).
  Article CAS PubMed Google Scholar
• Tachibana, T. et al. Increased intratumor Vα24-positive natural killer T cells: a prognostic factor for primary colorectal carcinomas. Clin. Cancer Res. 11, 7322–7327 (2005).
  Article CAS PubMed Google Scholar
• Schneiders, F. L. et al. Circulating invariant natural killer T-cell numbers predict outcome in head and neck squamous cell carcinoma: updated analysis with 10-year follow-up. J. Clin. Oncol. 30, 567–570 (2012).
  Article PubMed Google Scholar
• Terabe, M. et al. A nonclassical non-Vα14Jα18 CD1d-restricted (type II) NKT cell is sufficient for down-regulation of tumor immunosurveillance. J. Exp. Med. 202, 1627–1633 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Kawano, T. et al. Natural killer-like nonspecific tumor cell lysis mediated by specific ligand-activated Vα14 NKT cells. Proc. Natl Acad. Sci. USA 95, 5690–5693 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Parekh, V. V. et al. Glycolipid antigen induces long-term natural killer T cell anergy in mice. J. Clin. Invest. 115, 2572–2583 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Kim, S. et al. Impact of bacteria on the phenotype, functions, and therapeutic activities of invariant NKT cells in mice. J. Clin. Invest. 118, 2301–2315 (2008).
  CAS PubMed PubMed Central Google Scholar
• Cerundolo, V., Barral, P. & Batista, F. D. Synthetic iNKT cell-agonists as vaccine adjuvants — finding the balance. Curr. Opin. Immunol. 22, 417–424 (2010).
  Article CAS PubMed Google Scholar
• Stanic, A. K. et al. Another view of T cell antigen recognition: cooperative engagement of glycolipid antigens by Va14Ja18 natural T (iNKT) cell receptor. J. Immunol. 171, 4539–4551 (2003).
  Article CAS PubMed Google Scholar
• Oki, S., Tomi, C., Yamamura, T. & Miyake, S. Preferential Th2 polarization by OCH is supported by incompetent NKT cell induction of CD40L and following production of inflammatory cytokines by bystander cells in vivo. Int. Immunol. 17, 1619–1629 (2005).
  Article CAS PubMed Google Scholar
• Im, J. S. et al. Kinetics and cellular site of glycolipid loading control the outcome of natural killer T cell activation. Immunity 30, 888–898 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Sullivan, B. A. et al. Mechanisms for glycolipid antigen-driven cytokine polarization by Vα14i NKT cells. J. Immunol. 184, 141–153 (2010).
  Article CAS PubMed Google Scholar
• Yue, S. C. et al. Direct CD1d-mediated stimulation of APC IL-12 production and protective immune response to virus infection in vivo. J. Immunol. 184, 268–276 (2010).
  Article CAS PubMed Google Scholar
• Teng, M. W., Yue, S., Sharkey, J., Exley, M. A. & Smyth, M. J. CD1d activation and blockade: a new antitumor strategy. J. Immunol. 182, 3366–3371 (2009).
  Article CAS PubMed Google Scholar
• Hix, L. M. et al. CD1d-expressing breast cancer cells modulate NKT cell-mediated antitumor immunity in a murine model of breast cancer metastasis. PLoS ONE 6, e20702 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Barral, P. et al. B cell receptor-mediated uptake of CD1d-restricted antigen augments antibody responses by recruiting invariant NKT cell help in vivo. Proc. Natl Acad. Sci. USA 105, 8345–8350 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Barral, P. et al. CD169+ macrophages present lipid antigens to mediate early activation of _i_NKT cells in lymph nodes. Nature Immunol. 11, 303–312 (2010).
  Article CAS Google Scholar
• Motohashi, S. et al. A phase I study of in vitro expanded natural killer T cells in patients with advanced and recurrent non-small cell lung cancer. Clin. Cancer Res. 12, 6079–6086 (2006).
  Article CAS PubMed Google Scholar
• Yamasaki, K. et al. Induction of NKT cell-specific immune responses in cancer tissues after NKT cell-targeted adoptive immunotherapy. Clin. Immunol. 138, 255–265 (2011).
  Article CAS PubMed Google Scholar
• Giaccone, G. et al. A phase I study of the natural killer T-cell ligand α-galactosylceramide (KRN7000) in patients with solid tumors. Clin. Cancer Res. 8, 3702–3709 (2002).
  CAS PubMed Google Scholar
• Schneiders, F. L. et al. Clinical experience with α-galactosylceramide (KRN7000) in patients with advanced cancer and chronic hepatitis B/C infection. Clin. Immunol. 140, 130–141 (2011).
  Article CAS PubMed Google Scholar
• Nieda, M. et al. Therapeutic activation of Vα24+Vβ11+ NKT cells in human subjects results in highly coordinated secondary activation of acquired and innate immunity. Blood 103, 383–389 (2004).
  Article CAS PubMed Google Scholar
• Ishikawa, A. et al. A phase I study of α-galactosylceramide (KRN7000)-pulsed dendritic cells in patients with advanced and recurrent non-small cell lung cancer. Clin. Cancer Res. 11, 1910–1917 (2005).
  Article CAS PubMed Google Scholar
• Chang, D. H. et al. Sustained expansion of NKT cells and antigen-specific T cells after injection of α-galactosyl-ceramide loaded mature dendritic cells in cancer patients. J. Exp. Med. 201, 1503–1517 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Kunii, N. et al. Combination therapy of _in vitro_-expanded natural killer T cells and α-galactosylceramide-pulsed antigen-presenting cells in patients with recurrent head and neck carcinoma. Cancer Sci. 100, 1092–1098 (2009).
  Article CAS PubMed Google Scholar
• Cooper, M. A. et al. Cytokine-induced memory-like natural killer cells. Proc. Natl Acad. Sci. USA 106, 1915–1919 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Paust, S. et al. Critical role for the chemokine receptor CXCR6 in NK cell-mediated antigen-specific memory of haptens and viruses. Nature Immunol. 11, 1127–1135 (2010).
  Article CAS Google Scholar
• O'Leary, J. G., Goodarzi, M., Drayton, D. L. & von Andrian, U. H. T cell- and B cell-independent adaptive immunity mediated by natural killer cells. Nature Immunol. 7, 507–516 (2006).
  Article CAS Google Scholar
• Bukowski, J. F., Biron, C. A. & Welsh, R. M. Elevated natural killer cell-mediated cytotoxicity, plasma interferon, and tumor cell rejection in mice persistently infected with lymphocytic choriomeningitis virus. J. Immunol. 131, 991–996 (1983).
  CAS PubMed Google Scholar
• Carnaud, C. et al. Cutting edge: cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells. J. Immunol. 163, 4647–4650 (1999).
  CAS PubMed Google Scholar
• Eberl, G. & MacDonald, H. R. Selective induction of NK cell proliferation and cytotoxicity by activated NKT cells. Eur. J. Immunol. 30, 985–992 (2000).
  Article CAS PubMed Google Scholar
• Hermans, I. F. et al. NKT cells enhance CD4+ and CD8+ T cell responses to soluble antigen in vivo through direct interaction with dendritic cells. J. Immunol. 171, 5140–5147 (2003).
  Article CAS PubMed Google Scholar
• Wesley, J. D. et al. Cutting edge: IFN-γ signaling to macrophages is required for optimal Vα14i NK T/NK cell cross-talk. J. Immunol. 174, 3864–3868 (2005).
  Article CAS PubMed Google Scholar
• Gonzalez-Aseguinolaza, G. et al. Natural killer T cell ligand α-galactosylceramide enhances protective immunity induced by malaria vaccines. J. Exp. Med. 195, 617–624 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Huang, Y. et al. Enhancement of HIV DNA vaccine immunogenicity by the NKT cell ligand, α-galactosylceramide. Vaccine 26, 1807–1816 (2008).
  Article CAS PubMed Google Scholar
• Galli, G. et al. Invariant NKT cells sustain specific B cell responses and memory. Proc. Natl Acad. Sci. USA 104, 3984–3989 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Kamijuku, H. et al. Mechanism of NKT cell activation by intranasal coadministration of α-galactosylceramide, which can induce cross-protection against influenza viruses. Mucosal Immunol. 1, 208–218 (2008).
  Article CAS PubMed Google Scholar
• Miyamoto, K., Miyake, S. & Yamamura, T. A synthetic glycolipid prevents autoimmune encephalomyelitis by inducing TH2 bias of natural killer T cells. Nature 413, 531–534 (2001).
  Article CAS PubMed Google Scholar
• Oki, S., Chiba, A., Yamamura, T. & Miyake, S. The clinical implication and molecular mechanism of preferential IL-4 production by modified glycolipid-stimulated NKT cells. J. Clin. Invest. 113, 1631–1640 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Yu, K. O. et al. Modulation of CD1d-restricted NKT cell responses by using _N_-acyl variants of α-galactosylceramides. Proc. Natl Acad. Sci. USA 102, 3383–3388 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Schmieg, J., Yang, G., Franck, R. W. & Tsuji, M. Superior protection against malaria and melanoma metastases by a C-glycoside analogue of the natural killer T cell ligand α-galactosylceramide. J. Exp. Med. 198, 1631–1641 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Chiche, L. et al. The role of natural killer cells in sepsis. J. Biomed. Biotechnol. 2011, 986491 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Schleinitz, N., Vely, F., Harle, J. R. & Vivier, E. Natural killer cells in human autoimmune diseases. Immunology 131, 451–458 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Andrews, D. M. et al. Innate immunity defines the capacity of antiviral T cells to limit persistent infection. J. Exp. Med. 207, 1333–1343 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Waggoner, S. N., Cornberg, M., Selin, L. K. & Welsh, R. M. Natural killer cells act as rheostats modulating antiviral T cells. Nature 481, 394–398 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646–674 (2011).
  Article CAS PubMed Google Scholar
• Ogino, S., Galon, J., Fuchs, C. S. & Dranoff, G. Cancer immunology-analysis of host and tumor factors for personalized medicine. Nature Rev. Clin. Oncol. 8, 711–719 (2011).
  Article CAS Google Scholar
• Benlagha, K., Weiss, A., Beavis, A., Teyton, L. & Bendelac, A. In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. J. Exp. Med. 191, 1895–1903 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Matsuda, J. L. et al. Tracking the response of natural killer T cells to a glycolipid antigen using CD1d tetramers. J. Exp. Med. 192, 741–754 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Exley, M. A. et al. Selective activation, expansion, and monitoring of human iNKT cells with a monoclonal antibody specific for the TCR α-chain CDR3 loop. Eur. J. Immunol. 38, 1756–1766 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Pellicci, D. G. et al. Recognition of β-linked self glycolipids mediated by natural killer T cell antigen receptors. Nature Immunol. 12, 827–833 (2011). This study describes a previously unknown population of CD1d-restricted NKT cells.
  Article CAS Google Scholar
• Brennan, P. J. et al. Invariant natural killer T cells recognize lipid self antigen induced by microbial danger signals. Nature Immunol. 12, 1202–1211 (2011). This study shows that the expression of a newly identified endogenous ligand for the NKT cell TCR is increased during some infections and promotes NKT cell activation.
  Article CAS Google Scholar
• Brigl, M., Bry, L., Kent, S. C., Gumperz, J. E. & Brenner, M. B. Mechanism of CD1d-restricted natural killer T cell activation during microbial infection. Nature Immunol. 4, 1230–1237 (2003).
  Article CAS Google Scholar
• Mattner, J. et al. Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections. Nature 434, 525–529 (2005).
  Article CAS PubMed Google Scholar
• Salio, M. et al. Modulation of human natural killer T cell ligands on TLR-mediated antigen-presenting cell activation. Proc. Natl Acad. Sci. USA 104, 20490–20495 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Paget, C. et al. Activation of invariant NKT cells by Toll-like receptor 9-stimulated dendritic cells requires type I interferon and charged glycosphingolipids. Immunity 27, 597–609 (2007).
  Article CAS PubMed Google Scholar
• Kärre, K., Ljunggren, H. G., Piontek, G. & Kiessling, R. Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defense strategy. Nature 319, 675–678 (1986).
  Article PubMed Google Scholar
• Ljunggren, H. G. & Karre, K. In search of the 'missing self': MHC molecules and NK cell recognition. Immunol. Today 11, 237–244 (1990).
  Article CAS PubMed Google Scholar
• Moretta, L. et al. Allorecognition by NK cells: nonself or no self? Immunol Today 13, 300–306 (1992).
  Article CAS PubMed Google Scholar
• Karlhofer, F. M., Ribaudo, R. K. & Yokoyama, W. M. MHC class I alloantigen specificity of Ly-49+ IL-2-activated natural killer cells. Nature 358, 66–70 (1992).
  Article CAS PubMed Google Scholar
• Moretta, A. et al. Receptors for HLA class-I molecules in human natural killer cells. Annu. Rev. Immunol. 14, 619–648 (1996).
  Article CAS PubMed Google Scholar
• Kärre, K. How to recognize a foreign submarine. Immunol. Rev. 155, 5–9 (1997).
  Article PubMed Google Scholar
• Braud, V. M. et al. HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature 391, 795–799 (1998).
  Article CAS PubMed Google Scholar
• Vance, R. E., Kraft, J. R., Altman, J. D., Jensen, P. E. & Raulet, D. H. Mouse CD94/NKG2A is a natural killer cell receptor for the nonclassical major histocompatibility complex (MHC) class I molecule Qa-1b. J. Exp. Med. 188, 1841–1848 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Vilches, C. & Parham, P. KIR: diverse, rapidly evolving receptors of innate and adaptive immunity. Annu. Rev. Immunol. 20, 217–251 (2002).
  Article CAS PubMed Google Scholar
• Olcese, L. et al. Human and mouse killer-cell inhibitory receptors recruit PTP1C and PTP1D protein tyrosine phosphatases. J. Immunol. 156, 4531–4534 (1996).
  CAS PubMed Google Scholar
• Burshtyn, D. N. et al. Recruitment of tyrosine phosphatase HCP by the killer cell inhibitory receptor. Immunity 4, 77–85 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Vivier, E., Nunes, J. A. & Vely, F. Natural killer cell signaling pathways. Science 306, 1517–1519 (2004).
  Article CAS PubMed Google Scholar
• Kumar, V. & McNerney, M. E. A new self: MHC-class-I-independent natural-killer-cell self-tolerance. Nature Rev. Immunol. 5, 363–374 (2005).
  Article CAS Google Scholar