Tolerogenic dendritic cells and the quest for transplant tolerance (original) (raw)

• Banchereau, J. & Steinman, R. M. Dendritic cells and the control of immunity. Nature 392, 245–252 (1998).
  Article CAS PubMed Google Scholar
• Steinman, R. M., Hawiger, D. & Nussenzweig, M. C. Tolerogenic dendritic cells. Annu. Rev. Immunol. 21, 685–711 (2003).
  Article CAS PubMed Google Scholar
• Shortman, K. & Naik, S. H. Steady-state and inflammatory dendritic-cell development. Nature Rev. Immunol. 7, 19–30 (2007). References 2 and 3 are comprehensive and authoritative reviews of DC subsets and DC tolerogenicity.
  Article CAS Google Scholar
• Vremec, D., Pooley, J., Hochrein, H., Wu, L. & Shortman, K. CD4 and CD8 expression by dendritic cell subtypes in mouse thymus and spleen. J. Immunol. 164, 2978–2986 (2000).
  Article CAS PubMed Google Scholar
• Henri, S. et al. The dendritic cell populations of mouse lymph nodes. J. Immunol. 167, 741–748 (2001).
  Article CAS PubMed Google Scholar
• Corcoran, L. et al. The lymphoid past of mouse plasmacytoid cells and thymic dendritic cells. J. Immunol. 170, 4926–4932 (2003).
  Article CAS PubMed Google Scholar
• Shortman, K. & Liu, Y. J. Mouse and human dendritic cell subtypes. Nature Rev. Immunol. 2, 151–161 (2002).
  Article CAS Google Scholar
• Asselin-Paturel, C. et al. Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology. Nature Immunol. 2, 1144–1150 (2001).
  Article CAS Google Scholar
• Nakano, H., Yanagita, M. & Gunn, M. D. CD11c+B220+Gr-1+ cells in mouse lymph nodes and spleen display characteristics of plasmacytoid dendritic cells. J. Exp. Med. 194, 1171–1178 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Bjorck, P. Isolation and characterization of plasmacytoid dendritic cells from Flt3 ligand and granulocyte–macrophage colony-stimulating factor-treated mice. Blood 98, 3520–3526 (2001).
  Article CAS PubMed Google Scholar
• Yrlid, U. & Macpherson, G. Phenotype and function of rat dendritic cell subsets. APMIS 111, 756–765 (2003).
  Article CAS PubMed Google Scholar
• Brocker, T., Riedinger, M. & Karjalainen, K. Targeted expression of major histocompatibility complex (MHC) class II molecules demonstrates that dendritic cells can induce negative but not positive selection of thymocytes in vivo. J. Exp. Med. 185, 541–550 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Menges, M. et al. Repetitive injections of dendritic cells matured with tumor necrosis factor α induce antigen-specific protection of mice from autoimmunity. J. Exp. Med. 195, 15–21 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Verginis, P., Li, H. S. & Carayanniotis, G. Tolerogenic semimature dendritic cells suppress experimental autoimmune thyroiditis by activation of thyroglobulin-specific CD4+CD25+ T cells. J. Immunol. 174, 7433–7439 (2005).
  Article CAS PubMed Google Scholar
• Hackstein, H. & Thomson, A. W. Dendritic cells: emerging pharmacological targets of immunosuppressive drugs. Nature Rev. Immunol. 4, 24–35 (2004). A detailed survey of how pharmacological agents regulate DC differentiation and maturation and promote their tolerogenic properties.
  Article CAS Google Scholar
• Morelli, A. E. & Thomson, A. W. Dendritic cells: regulators of alloimmunity and opportunities for tolerance induction. Immunol. Rev. 196, 125–146 (2003).
  Article CAS PubMed Google Scholar
• Chauveau, C. et al. Heme oxygenase-1 expression inhibits dendritic cell maturation and proinflammatory function but conserves IL-10 expression. Blood 106, 1694–1702 (2005).
  Article CAS PubMed Google Scholar
• Hackstein, H. et al. Rapamycin inhibits IL-4-induced dendritic cell maturation in vitro and dendritic cell mobilization and function in vivo. Blood 101, 4457–4463 (2003).
  Article CAS PubMed Google Scholar
• Turnquist, H. et al. Rapamycin-conditioned dendritic cells are poor stimulators of allogeneic CD4+ T cells, but enrich for antigen-specific Foxp3+ T regulatory cells and promote organ transplant tolerance. J. Immunol. 178, 7018–7031 (2007).
  Article CAS PubMed Google Scholar
• Min, W. P. et al. Inhibitory feedback loop between tolerogenic dendritic cells and regulatory T cells in transplant tolerance. J. Immunol. 170, 1304–1312 (2003).
  Article CAS PubMed Google Scholar
• Penna, G. & Adorini, L. 1α, 25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J. Immunol. 164, 2405–2411 (2000).
  Article CAS PubMed Google Scholar
• Griffin, M. D. et al. Potent inhibition of dendritic cell differentiation and maturation by vitamin D analogs. Biochem. Biophys. Res. Commun. 270, 701–708 (2000).
  Article CAS PubMed Google Scholar
• Barrat, F. J. et al. In vitro generation of interleukin 10-producing regulatory CD4+ T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (TH1)- and TH2-inducing cytokines. J. Exp. Med. 195, 603–616 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Gregori, S. et al. Regulatory T cells induced by 1α, 25-dihydroxyvitamin D3 and mycophenolate mofetil treatment mediate transplantation tolerance. J. Immunol. 167, 1945–1953 (2001).
  Article CAS PubMed Google Scholar
• Liang, S. & Horuzsko, A. Mobilizing dendritic cells for tolerance by engagement of immune inhibitory receptors for HLA-G. Hum. Immunol. 64, 1025–1032 (2003).
  Article CAS PubMed Google Scholar
• Bonham, C. A. et al. Marked prolongation of cardiac allograft survival by dendritic cells genetically engineered with NF-κB oligodeoxyribonucleotide decoys and adenoviral vectors encoding CTLA4-Ig. J. Immunol. 169, 3382–3391 (2002).
  Article CAS PubMed Google Scholar
• Hill, J. A. et al. Immune modulation by silencing IL-12 production in dendritic cells using small interfering RNA. J. Immunol. 171, 691–696 (2003).
  Article CAS PubMed Google Scholar
• Maraskovsky, E. et al. Dramatic increase in the numbers of functionally mature dendritic cells in Flt3 ligand-treated mice: multiple dendritic cell subpopulations identified. J. Exp. Med. 184, 1953–1962 (1996).
  Article CAS PubMed Google Scholar
• Pulendran, B. et al. Prevention of peripheral tolerance by a dendritic cell growth factor: flt3 ligand as an adjuvant. J. Exp. Med. 188, 2075–2082 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Coates, P. T. et al. Dendritic cell subsets in blood and lymphoid tissue of rhesus monkeys and their mobilization with Flt3 ligand. Blood 102, 2513–2521 (2003).
  Article CAS PubMed Google Scholar
• Eto, M., Hackstein, H., Kaneko, K., Nomoto, K. & Thomson, A. W. Promotion of skin graft tolerance across MHC barriers by mobilization of dendritic cells in donor hemopoietic cell infusions. J. Immunol. 169, 2390–2396 (2002).
  Article CAS PubMed Google Scholar
• Antonysamy, M. A. et al. Flt-3 ligand increases microchimerism but can prevent the therapeutic effect of donor bone marrow in transiently immunosuppressed cardiac allograft recipients. J. Immunol. 160, 4106–4113 (1998).
  CAS PubMed Google Scholar
• Hackstein, H. et al. Normal donor bone marrow is superior to Flt3 ligand-mobilized bone marrow in prolonging heart allograft survival when combined with anti-CD40L (CD154). Am. J. Transplant. 2, 609–617 (2002).
  Article CAS PubMed Google Scholar
• Coates, P. T. et al. _In vivo_-mobilized kidney dendritic cells are functionally immature, subvert alloreactive T-cell responses, and prolong organ allograft survival. Transplantation 77, 1080–1089 (2004).
  Article PubMed Google Scholar
• Steptoe, R. J. et al. Augmentation of dendritic cells in murine organ donors by Flt3 ligand alters the balance between transplant tolerance and immunity. J. Immunol. 159, 5483–5491 (1997).
  CAS PubMed Google Scholar
• Arpinati, M., Green, C. L., Heimfeld, S., Heuser, J. E. & Anasetti, C. Granulocyte-colony stimulating factor mobilizes T helper 2-inducing dendritic cells. Blood 95, 2484–2490 (2000).
  CAS PubMed Google Scholar
• Gould, D. S. & Auchincloss, H. Jr. Direct and indirect recognition: the role of MHC antigens in graft rejection. Immunol. Today 20, 77–82 (1999).
  Article CAS PubMed Google Scholar
• Herrera, O. B. et al. A novel pathway of alloantigen presentation by dendritic cells. J. Immunol. 173, 4828–4837 (2004).
  Article CAS PubMed Google Scholar
• Thery, C. et al. Indirect activation of naive CD4+ T cells by dendritic cell-derived exosomes. Nature Immunol. 3, 1156–1162 (2002).
  Article CAS Google Scholar
• Harshyne, L. A., Watkins, S. C., Gambotto, A. & Barratt-Boyes, S. M. Dendritic cells acquire antigens from live cells for cross-presentation to CTL. J. Immunol. 166, 3717–3723 (2001).
  Article CAS PubMed Google Scholar
• Mueller, D. L., Jenkins, M. K. & Schwartz, R. H. Clonal expansion versus functional clonal inactivation: a costimulatory signalling pathway determines the outcome of T cell antigen receptor occupancy. Annu. Rev. Immunol. 7, 445–480 (1989).
  Article CAS PubMed Google Scholar
• Lu, L., McCaslin, D., Starzl, T. E. & Thomson, A. W. Bone marrow-derived dendritic cell progenitors (NLDC 145+, MHC class II+, B7-1dim, B7-2−) induce alloantigen-specific hyporesponsiveness in murine T lymphocytes. Transplantation 60, 1539–1545 (1995).
  Article CAS PubMed PubMed Central Google Scholar
• Fu, F. et al. Costimulatory molecule-deficient dendritic cell progenitors (MHC class II+, CD80dim, CD86−) prolong cardiac allograft survival in nonimmunosuppressed recipients. Transplantation 62, 659–665 (1996). The first account of the ability of immature myeloid DCs of donor origin to prolong organ allograft survival.
  Article CAS PubMed PubMed Central Google Scholar
• Lutz, M. B. et al. Immature dendritic cells generated with low doses of GM-CSF in the absence of IL-4 are maturation resistant and prolong allograft survival in vivo. Eur. J. Immunol. 30, 1813–1822 (2000). Describes how maturation-resistant DCs can induce indefinite organ allograft survival.
  Article CAS PubMed Google Scholar
• Cong, Y. et al. Generation of antigen-specific, Foxp3-expressing CD4+ regulatory T cells by inhibition of APC proteosome function. J. Immunol. 174, 2787–2795 (2005).
  Article CAS PubMed Google Scholar
• Wakkach, A. et al. Characterization of dendritic cells that induce tolerance and T regulatory 1 cell differentiation in vivo. Immunity 18, 605–617 (2003).
  Article CAS PubMed Google Scholar
• Yamazaki, S. et al. Direct expansion of functional CD25+ CD4+ regulatory T cells by antigen-processing dendritic cells. J. Exp. Med. 198, 235–247 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Yamazaki, S. et al. Effective expansion of alloantigen-specific Foxp3+ CD25+ CD4+ regulatory T cells by dendritic cells during the mixed leukocyte reaction. Proc. Natl Acad. Sci. USA 103, 2758–2763 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Tarbell, K. V., Yamazaki, S., Olson, K., Toy, P. & Steinman, R. M. CD25+ CD4+ T cells, expanded with dendritic cells presenting a single autoantigenic peptide, suppress autoimmune diabetes. J. Exp. Med. 199, 1467–1477 (2004). Shows that antigen-specific T Reg cells can be expanded in vitro using DCs and that these T Reg cells suppress autoimmune disease.
  Article CAS PubMed PubMed Central Google Scholar
• Rastellini, C. et al. Granulocyte/macrophage colony-stimulating factor-stimulated hepatic dendritic cell progenitors prolong pancreatic islet allograft survival. Transplantation 60, 1366–1370 (1995).
  CAS PubMed PubMed Central Google Scholar
• Lu, L. et al. Blockade of the CD40–CD40 ligand pathway potentiates the capacity of donor-derived dendritic cell progenitors to induce long-term cardiac allograft survival. Transplantation 64, 1808–1815 (1997).
  Article CAS PubMed Google Scholar
• Niimi, M. et al. Operational tolerance induced by pretreatment with donor dendritic cells under blockade of CD40 pathway. Transplantation 72, 1556–1562 (2001).
  Article CAS PubMed Google Scholar
• Hayamizu, K., Huie, P., Sibley, R. K. & Strober, S. Monocyte-derived dendritic cell precursors facilitate tolerance to heart allografts after total lymphoid irradiation. Transplantation 66, 1285–1291 (1998).
  Article CAS PubMed Google Scholar
• Selenko-Gebauer, N. et al. B7-H1 (programmed death-1 ligand) on dendritic cells is involved in the induction and maintenance of T cell anergy. J. Immunol. 170, 3637–3644 (2003).
  Article CAS PubMed Google Scholar
• Munn, D. H. et al. Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase. Science 297, 1867–1870 (2002).
  Article CAS PubMed Google Scholar
• Munn, D. H., Sharma, M. D. & Mellor, A. L. Ligation of B7-1/B7-2 by human CD4+ T cells triggers indoleamine 2,3-dioxygenase activity in dendritic cells. J. Immunol. 172, 4100–4110 (2004).
  Article CAS PubMed Google Scholar
• Chang, C. C. et al. Tolerization of dendritic cells by TS cells: the crucial role of inhibitory receptors ILT3 and ILT4. Nature Immunol. 3, 237–243 (2002).
  Article CAS Google Scholar
• Steinbrink, K., Graulich, E., Kubsch, S., Knop, J. & Enk, A. H. CD4+ and CD8+ anergic T cells induced by interleukin-10-treated human dendritic cells display antigen-specific suppressor activity. Blood 99, 2468–2476 (2002).
  Article CAS PubMed Google Scholar
• Jonuleit, H., Schmitt, E., Schuler, G., Knop, J. & Enk, A. H. Induction of interleukin 10-producing, nonproliferating CD4+ T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J. Exp. Med. 192, 1213–1222 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Levings, M. K. et al. Differentiation of TR1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ TR cells. Blood 105, 1162–1169 (2005).
  Article CAS PubMed Google Scholar
• Suss, G. & Shortman, K. A subclass of dendritic cells kills CD4 T cells via Fas/Fas-ligand- induced apoptosis. J. Exp. Med. 183, 1789–1796 (1996).
  Article CAS PubMed Google Scholar
• Belz, G. T. et al. The CD8α+ dendritic cell is responsible for inducing peripheral self-tolerance to tissue-associated antigens. J. Exp. Med. 196, 1099–1104 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Dudziak, D. et al. Differential antigen processing by dendritic cell subsets in vivo. Science 315, 107–111 (2007).
  Article CAS PubMed Google Scholar
• Grohmann, U. et al. CD40 ligation ablates the tolerogenic potential of lymphoid dendritic cells. J. Immunol. 166, 277–283 (2001).
  Article CAS PubMed Google Scholar
• Grohmann, U. et al. IFN-γ inhibits presentation of a tumor/self peptide by CD8α− dendritic cells via potentiation of the CD8α+ subset. J. Immunol. 165, 1357–1363 (2000).
  Article CAS PubMed Google Scholar
• Fallarino, F. et al. Modulation of tryptophan catabolism by regulatory T cells. Nature Immunol. 4, 1206–1212 (2003). An elegant demonstration that ligation of CTLA4 by T Reg cells on DCs augments functional IDO expression.
  Article CAS Google Scholar
• Belladonna, M. L. et al. Kynurenine pathway enzymes in dendritic cells initiate tolerogenesis in the absence of functional IDO. J. Immunol. 177, 130–137 (2006).
  Article CAS PubMed Google Scholar
• Grohmann, U. et al. CTLA-4-Ig regulates tryptophan catabolism in vivo. Nature Immunol. 3, 1097–1101 (2002).
  Article CAS Google Scholar
• Mellor, A. L. & Munn, D. H. IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nature Rev. Immunol. 4, 762–774 (2004).
  Article CAS Google Scholar
• O'Connell, P. J. et al. Immature and mature CD8α+ dendritic cells prolong the survival of vascularized heart allografts. J. Immunol. 168, 143–154 (2002).
  Article CAS PubMed Google Scholar
• Siegal, F. P. et al. The nature of the principal type 1 interferon-producing cells in human blood. Science 284, 1835–1837 (1999).
  Article CAS PubMed Google Scholar
• Kadowaki, N. et al. Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. J. Exp. Med. 194, 863–869 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Rissoan, M. C. et al. Reciprocal control of T helper cell and dendritic cell differentiation. Science 283, 1183–1186 (1999).
  Article CAS PubMed Google Scholar
• Moseman, E. A. et al. Human plasmacytoid dendritic cells activated by CpG oligodeoxynucleotides induce the generation of CD4+CD25+ regulatory T cells. J. Immunol. 173, 4433–4442 (2004).
  Article CAS PubMed Google Scholar
• Gilliet, M. & Liu, Y. J. Generation of human CD8 T regulatory cells by CD40 ligand-activated plasmacytoid dendritic cells. J. Exp. Med. 195, 695–704 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Ito, T. et al. Plasmacytoid dendritic cells prime IL-10-producing T regulatory cells by inducible costimulator ligand. J. Exp. Med. 204, 105–115 (2007). References 74–76 show how pDCs can generate different types of regulatory T cells.
  Article CAS PubMed PubMed Central Google Scholar
• Fallarino, F. et al. Murine plasmacytoid dendritic cells initiate the immunosuppressive pathway of tryptophan catabolism in response to CD200 receptor engagement. J. Immunol. 173, 3748–3754 (2004).
  Article CAS PubMed Google Scholar
• Grohmann, U. et al. Reverse signaling through GITR ligand enables dexamethasone to activate IDO in allergy. Nature Med. 13, 579–586 (2007).
  Article CAS PubMed Google Scholar
• Fugier-Vivier, I. J. et al. Plasmacytoid precursor dendritic cells facilitate allogeneic hematopoietic stem cell engraftment. J. Exp. Med. 201, 373–383 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Abe, M., Wang, Z., De Creus, A. & Thomson, A. W. Plasmacytoid dendritic cell precursors induce allogeneic T cell hyporesponsiveness and prolong heart graft survival. Am. J. Transplant. 5, 1808–1819 (2005).
  Article CAS PubMed Google Scholar
• Inaba, K. et al. Efficient presentation of phagocytosed cellular fragments on the major histocompatibility complex class II products of dendritic cells. J. Exp. Med. 188, 2163–2173 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Yu, G., Xu, X., Vu, M. D., Kilpatrick, E. D. & Li, X. C. NK cells promote transplant tolerance by killing donor antigen-presenting cells. J. Exp. Med. 203, 1851–1858 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Garrovillo, M., Ali, A. & Oluwole, S. F. Indirect allorecognition in acquired thymic tolerance: induction of donor-specific tolerance to rat cardiac allografts by allopeptide-pulsed host dendritic cells. Transplantation 68, 1827–1834 (1999). The first report that alloantigen-pulsed host DCs can be used to induce alloantigen-specific organ transplant tolerance.
  Article CAS PubMed Google Scholar
• Ali, A., Garrovillo, M., Jin, M. X., Hardy, M. A. & Oluwole, S. F. Major histocompatibility complex class I peptide-pulsed host dendritic cells induce antigen-specific acquired thymic tolerance to islet cells. Transplantation 69, 221–226 (2000).
  Article CAS PubMed Google Scholar
• Oluwole, O. O. et al. Indirect allorecognition in acquired thymic tolerance: induction of donor-specific permanent acceptance of rat islets by adoptive transfer of allopeptide-pulsed host myeloid and thymic dendritic cells. Diabetes 50, 1546–1552 (2001).
  Article CAS PubMed Google Scholar
• Taner, T., Hackstein, H., Wang, Z., Morelli, A. E. & Thomson, A. W. Rapamycin-treated, alloantigen-pulsed host dendritic cells induce Ag-specific T cell regulation and prolong graft survival. Am. J. Transplant. 5, 228–236 (2005).
  Article CAS PubMed Google Scholar
• Peche, H., Trinite, B., Martinet, B. & Cuturi, M. C. Prolongation of heart allograft survival by immature dendritic cells generated from recipient type bone marrow progenitors. Am. J. Transplant. 5, 255–267 (2005).
  Article PubMed Google Scholar
• Beriou, G., Peche, H., Guillonneau, C., Merieau, E. & Cuturi, M. C. Donor-specific allograft tolerance by administration of recipient-derived immature dendritic cells and suboptimal immunosuppression. Transplantation 79, 969–972 (2005).
  Article CAS PubMed Google Scholar
• Sato, K., Yamashita, N., Yamashita, N., Baba, M. & Matsuyama, T. Regulatory dendritic cells protect mice from murine acute graft-versus-host disease and leukemia relapse. Immunity 18, 367–379 (2003).
  Article CAS PubMed Google Scholar
• Golshayan, D. et al. _In vitro_-expanded donor alloantigen-specific CD4+CD25+ regulatory T cells promote experimental transplantation tolerance. Blood 109, 827–835 (2007). This study shows that DCs can expand alloantigen-specific T Reg cells in vitro that promote transplant tolerance.
  Article CAS PubMed Google Scholar
• Jiang, S., Camara, N., Lombardi, G. & Lechler, R. I. Induction of allopeptide-specific human CD4+CD25+ regulatory T cells ex vivo. Blood 102, 2180–2186 (2003).
  Article CAS PubMed Google Scholar
• Dhodapkar, M. V., Steinman, R. M., Krasovsky, J., Munz, C. & Bhardwaj, N. Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J. Exp. Med. 193, 233–238 (2001). A proof-of-principle study that shows that immature autologous DCs pulsed with nominal antigen can induce antigen-specific T-cell tolerance in healthy volunteers.
  Article CAS PubMed PubMed Central Google Scholar
• Ochando, J. C. et al. Alloantigen-presenting plasmacytoid dendritic cells mediate tolerance to vascularized grafts. Nature Immunol. 7, 652–662 (2006).
  Article CAS Google Scholar
• Baban, B. et al. A minor population of splenic dendritic cells expressing CD19 mediates IDO-dependent T cell suppression via type I IFN signaling following B7 ligation. Int. Immunol. 17, 909–919 (2005).
  Article CAS PubMed Google Scholar
• Mellor, A. L. et al. Specific subsets of murine dendritic cells acquire potent T cell regulatory functions following CTLA4-mediated induction of indoleamine 2,3 dioxygenase. Int. Immunol. 16, 1391–1401 (2004).
  Article CAS PubMed Google Scholar
• Mellor, A. L. et al. Cutting edge: CpG oligonucleotides induce splenic CD19+ dendritic cells to acquire potent indoleamine 2,3-dioxygenase-dependent T cell regulatory functions via IFN Type 1 signaling. J. Immunol. 175, 5601–5605 (2005).
  Article CAS PubMed Google Scholar
• Mirenda, V. et al. Modified dendritic cells coexpressing self and allogeneic major histocompatibility complex molecules: an efficient way to induce indirect pathway regulation. J. Am. Soc. Nephrol. 15, 987–997 (2004).
  Article CAS PubMed Google Scholar
• Garrod, K. R. et al. Targeted lymphoid homing of dendritic cells is required for prolongation of allograft survival. J. Immunol. 177, 863–868 (2006).
  Article CAS PubMed Google Scholar
• Matsue, H. et al. Immunosuppressive properties of CD95L-transduced 'killer' hybrids created by fusing donor- and recipient-derived dendritic cells. Blood 98, 3465–3472 (2001).
  Article CAS PubMed Google Scholar
• Morelli, A. E. The immune regulatory effect of apoptotic cells and exosomes on dendritic cells: its impact on transplantation. Am. J. Transplant. 6, 254–261 (2006).
  Article CAS PubMed Google Scholar
• Hawiger, D. et al. Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J. Exp. Med. 194, 769–779 (2001). The first documentation that in situ targeting of DCs with monoclonal antibodies and antigen in the steady state is associated with antigen-specific T-cell tolerance.
  Article CAS PubMed PubMed Central Google Scholar
• Bonifaz, L. et al. Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance. J. Exp. Med. 196, 1627–1638 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Larregina, A. T. & Morelli, A. E. in Handbook of Dendritic Dells: Biology, Diseases, and Therapies (eds Lutz, M. B., Romani, N. & Steinkasserer, A.) 591–618 (Wiley-VCH, Weinheim, 2006).
  Book Google Scholar
• Morelli, A. E. et al. Internalization of circulating apoptotic cells by splenic marginal zone dendritic cells: dependence on complement receptors and effect on cytokine production. Blood 101, 611–620 (2003).
  Article CAS PubMed Google Scholar
• Wang, Z. et al. Use of the inhibitory effect of apoptotic cells on dendritic cells for graft survival via T-cell deletion and regulatory T cells. Am. J. Transplant. 6, 1297–1311 (2006). The first report that in situ targeting of DCs with donor-derived apoptotic cells prolongs solid organ allograft survival.
  Article CAS PubMed Google Scholar
• Thery, C., Zitvogel, L. & Amigorena, S. Exosomes: composition, biogenesis and function. Nature Rev. Immunol. 2, 569–579 (2002).
  Article CAS Google Scholar
• Morelli, A. E. et al. Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells. Blood 104, 3257–3266 (2004).
  Article CAS PubMed Google Scholar
• Peche, H. et al. Induction of tolerance by exosomes and short-term immunosuppression in a fully MHC-mismatched rat cardiac allograft model. Am. J. Transplant. 6, 1541–1550 (2006).
  Article CAS PubMed Google Scholar
• Qian, S., Thai, N. L., Lu, L., Fung, J. J. & Thomson, A. W. Liver transplant tolerance: mechanistic insights from animal models with particular reference to the mouse. Transplant. Rev. 11, 151–164 (1997).
  Article Google Scholar
• Crispe, I. N. Hepatic T cells and liver tolerance. Nature Rev. Immunol. 3, 51–62 (2003).
  Article CAS Google Scholar
• Pillarisetty, V. G., Miller, G., Shah, A. B. & DeMatteo, R. P. GM-CSF expands dendritic cells and their progenitors in mouse liver. Hepatology 37, 641–652 (2003).
  Article CAS PubMed Google Scholar
• Sun, J., McCaughan, G. W., Gallagher, N. D., Sheil, A. G. & Bishop, G. A. Deletion of spontaneous rat liver allograft acceptance by donor irradiation. Transplantation 60, 233–236 (1995).
  Article CAS PubMed Google Scholar
• Shimizu, Y. et al. Restoration of tolerance to rat hepatic allografts by spleen-derived passenger leukocytes. Transpl. Int. 9, 593–595 (1996).
  Article CAS PubMed Google Scholar
• Lu, L. et al. Growth of donor-derived dendritic cells from the bone marrow of murine liver allgraft recipients in response to granulocyte/macrophage colony stimulating factor. J. Exp. Med. 182, 379–387 (1995). The novel finding that donor-derived DCs can be propagated from the bone marrow of animals that show spontaneous liver transplant tolerance but not from those that acutely reject heart allografts.
  Article CAS PubMed Google Scholar
• Demetris, A. et al. Analysis of chronic rejection and obliterative arteriolopathy. Possible contributions of donor antigen presenting cells and lymphatic disruption. Am. J. Pathol. 150, 563 (1997).
  CAS PubMed PubMed Central Google Scholar
• Qian, S. et al. Apoptosis within spontaneously accepted mouse liver allografts: evidence for deletion of cytotoxic T cells and implications for tolerance induction. J. Immunol. 158, 4654–4661 (1997).
  CAS PubMed Google Scholar
• Sharland, A. et al. Evidence that apoptosis of activated T cells occurs in spontaneous tolerance of liver allografts and is blocked by manipulations which break tolerance. Transplantation 68, 1736–1745 (1999).
  Article CAS PubMed Google Scholar
• Li, W. et al. IL-12 antagonism enhances apoptotic death of T cells within hepatic allografts from Flt3 ligand-treated donors and promotes graft acceptance. J. Immunol. 166, 5619–5628 (2001).
  Article CAS PubMed Google Scholar
• Randow, F. et al. Mechanism of endotoxin desensitization: involvement of interleukin 10 and transforming growth factor β. J. Exp. Med. 181, 1887–1892 (1995).
  Article CAS PubMed Google Scholar
• van der Poll, T., Coyle, S. M., Moldawer, L. L. & Lowry, S. F. Changes in endotoxin-induced cytokine production by whole blood after in vivo exposure of normal humans to endotoxin. J. Infect. Dis. 174, 1356–1360 (1996).
  Article CAS PubMed Google Scholar
• Dobrovolskaia, M. A. & Vogel, S. N. Toll receptors, CD14, and macrophage activation and deactivation by LPS. Microbes Infect. 4, 903–914 (2002).
  Article CAS PubMed Google Scholar
• Kobayashi, K. et al. IRAK-M is a negative regulator of Toll-like receptor signaling. Cell 110, 191–202 (2002).
  Article CAS PubMed Google Scholar
• Medvedev, A. E., Lentschat, A., Wahl, L. M., Golenbock, D. T. & Vogel, S. N. Dysregulation of LPS-induced Toll-like receptor 4–MyD88 complex formation and IL-1 receptor-associated kinase 1 activation in endotoxin-tolerant cells. J. Immunol. 169, 5209–5216 (2002).
  Article PubMed Google Scholar
• Nakagawa, R. et al. SOCS-1 participates in negative regulation of LPS responses. Immunity 17, 677–687 (2002).
  Article CAS PubMed Google Scholar
• Ziegler-Heitbrock, H. W. Molecular mechanism in tolerance to lipopolysaccharide. J. Inflamm. 45, 13–26 (1995).
  CAS PubMed Google Scholar
• Wysocka, M. et al. IL-12 suppression during experimental endotoxin tolerance: dendritic cell loss and macrophage hyporesponsiveness. J. Immunol. 166, 7504–7513 (2001).
  Article CAS PubMed Google Scholar
• Tinsley, K. W. et al. Sepsis induces apoptosis and profound depletion of splenic interdigitating and follicular dendritic cells. J. Immunol. 171, 909–914 (2003).
  Article CAS PubMed Google Scholar
• De Creus, A. et al. Low TLR4 expression by liver dendritic cells correlates with reduced capacity to activate allogeneic T cells in response to endotoxin. J. Immunol. 174, 2037–2045 (2005).
  Article CAS PubMed Google Scholar
• Abe, M., Tokita, D., Raimondi, G. & Thomson, A. W. Endotoxin modulates the capacity of CpG-activated liver myeloid DC to direct TH1-type responses. Eur. J. Immunol. 36, 2483–2493 (2006).
  Article CAS PubMed Google Scholar
• Ishiyama, K. et al. Induction of endotoxin tolerance inhibits alloimmune responses. Transpl. Immunol. 16, 158–165 (2006).
  Article CAS PubMed Google Scholar
• Liew, F. Y., Xu, D., Brint, E. K. & O'Neill L, A. Negative regulation of Toll-like receptor-mediated immune responses. Nature Rev. Immunol. 5, 446–458 (2005).
  Article CAS Google Scholar