Steinman, R. M. The dendritic cell system and its role in immunogenicity. Annu. Rev. Immunol.9, 271–296 (1991). ArticleCASPubMed Google Scholar
Steinman, R. M. & Nussenzweig, M. C. Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc. Natl Acad. Sci. USA99, 351–358 (2002). CASPubMedPubMed Central Google Scholar
Steinman, R. M. & Witmer, M. D. Lymphoid dendritic cells are potent stimulators of the primary mixed leukocyte reaction in mice. Proc. Natl Acad. Sci. USA75, 5132–5136 (1978). CASPubMedPubMed Central Google Scholar
Nussenzweig, M. C., Steinman, R. M., Gutchinov, B. & Cohn, Z. A. Dendritic cells are accessory cells for the development of anti-trinitrophenyl cytotoxic T lymphocytes. J. Exp. Med.152, 1070–1084 (1980). CASPubMed Google Scholar
Van Voorhis, W. C. et al. Relative efficacy of human monocytes and dendritic cells as accessory cells for T cell replication. J. Exp. Med.158, 174–191 (1983). CASPubMed Google Scholar
Inaba, K. & Steinman, R. M. Resting and sensitized T lymphocytes exhibit distinct stimulatory (antigen-presenting cell) requirements for growth and lymphokine release. J. Exp. Med.160, 1717–1735 (1984). CASPubMed Google Scholar
Schuler, G. & Steinman, R. M. Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro. J. Exp. Med.161, 526–546 (1985). CASPubMed Google Scholar
Romani, N. et al. Presentation of exogenous protein antigens by dendritic cells to T cell clones. Intact protein is presented best by immature, epidermal Langerhans cells. J. Exp. Med.169, 1169–1178 (1989). CASPubMed Google Scholar
Romani, N. et al. A small number of anti-CD3 molecules on dendritic cells stimulate DNA synthesis in mouse T lymphocytes. J. Exp. Med.169, 1153–1168 (1989). CASPubMed Google Scholar
Austyn, J. M., Kupiec-Weglinski, J. W., Hankins, D. F. & Morris, P. J. Migration patterns of dendritic cells in the mouse. Homing to T cell-dependent areas of spleen, and binding within marginal zone. J. Exp. Med.167, 646–651 (1988). CASPubMed Google Scholar
Larsen, C. et al. Migration and maturation of Langerhans cells in skin transplants and explants. J. Exp. Med.172, 1483–1493 (1990). CASPubMed Google Scholar
Reis e Sousa, C., Stahl, P. D. & Austyn, J. M. Phagocytosis of antigens by Langerhans cells in vitro. J. Exp. Med.178, 509–519 (1993). CASPubMed Google Scholar
Villadangos, J. A. & Heath, W. R. Life cycle, migration and antigen presenting functions of spleen and lymph node dendritic cells: limitations of the Langerhans cells paradigm. Semin. Immunol.17, 262–272 (2005). CASPubMed Google Scholar
Larsen, C. P., Ritchie, S. C., Pearson, T. C., Linsley, P. S. & Lowry, R. P. Functional expression of the costimulatory molecule, B7/BB1, on murine dendritic cell populations. J. Exp. Med.176, 1215–1220 (1992). CASPubMed Google Scholar
Inaba, K. et al. The tissue distribution of the B7–2 costimulator in mice: abundant expression on dendritic cells in situ and during maturation in vitro. J. Exp. Med.180, 1849–1860 (1994). CASPubMed Google Scholar
Inaba, K. et al. Immunologic properties of purified epidermal Langerhans cells: distinct requirements for stimulation of unprimed and sensitized T lymphocytes. J. Exp. Med.164, 605–613 (1986). CASPubMed Google Scholar
Sallusto, F. & Lanzavecchia, A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor α. J. Exp. Med.179, 1109–1118 (1994). CASPubMed Google Scholar
Winzler, C. et al. Maturation stages of mouse dendritic cells in growth factor-dependent long-term cultures. J. Exp. Med.185, 317–328 (1997). CASPubMedPubMed Central Google Scholar
Roake, J. A. et al. Dendritic cell loss from nonlymphoid tissues after systemic administration of lipopolysaccharide, tumor necrosis factor, and interleukin 1. J. Exp. Med.181, 2237–2247 (1995). CASPubMed Google Scholar
De Smedt, T. et al. Regulation of dendritic cell numbers and maturation by lipopolysaccharide in vivo. J. Exp. Med.184, 1413–1424 (1996). CASPubMed Google Scholar
Janeway, C. A. Jr. Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb. Symp. Quant. Biol.54, 1–13 (1989). CASPubMed Google Scholar
Matzinger, P. Tolerance, danger, and the extended family. Annu. Rev. Immunol.12, 991–1045 (1994). CASPubMed Google Scholar
Pierre, P. & Mellman, I. Developmental regulation of invariant chain proteolysis controls MHC class II trafficking in mouse dendritic cells. Cell93, 1135–1145 (1998). CASPubMed Google Scholar
Inaba, K. et al. The formation of immunogenic major histocompatibility complex class II–peptide ligands in lysosomal compartments of dendritic cells is regulated by inflammatory stimuli. J. Exp. Med.191, 927–936 (2000). CASPubMedPubMed Central Google Scholar
Manickasingham, S. & Reis e Sousa, C. Microbial and T cell-derived stimuli regulate antigen presentation by dendritic cells in vivo. J. Immunol.165, 5027–5034 (2000). CASPubMed Google Scholar
Trombetta, E. S., Ebersold, M., Garrett, W., Pypaert, M. & Mellman, I. Activation of lysosomal function during dendritic cell maturation. Science299, 1400–1403 (2003). CASPubMed Google Scholar
Delamarre, L., Holcombe, H. & Mellman, I. Presentation of exogenous antigens on major histocompatibility complex (MHC) class I and MHC class II molecules is differentially regulated during dendritic cell maturation. J. Exp. Med.198, 111–122 (2003). CASPubMedPubMed Central Google Scholar
Gil-Torregrosa, B. C. et al. Control of cross-presentation during dendritic cell maturation. Eur. J. Immunol.34, 398–407 (2004). CASPubMed Google Scholar
West, M. A. et al. Enhanced dendritic cell antigen capture via toll-like receptor-induced actin remodeling. Science305, 1153–1157 (2004). ArticleCASPubMed Google Scholar
Wilson, N. S. & Villadangos, J. A. Lymphoid organ dendritic cells: beyond the Langerhans cells paradigm. Immunol. Cell Biol.82, 91–98 (2004). PubMed Google Scholar
Allan, R. S. et al. Epidermal viral immunity induced by CD8α+ dendritic cells but not by Langerhans cells. Science301, 1925–1928 (2003). CASPubMed Google Scholar
Zhao, X. et al. Vaginal submucosal dendritic cells, but not Langerhans cells, induce protective Th1 responses to herpes simplex virus-2. J. Exp. Med.197, 153–162 (2003). CASPubMedPubMed Central Google Scholar
Itano, A. A. et al. Distinct dendritic cell populations sequentially present antigen to CD4 T cells and stimulate different aspects of cell-mediated immunity. Immunity19, 47–57 (2003). CASPubMed Google Scholar
Carbone, F. R., Belz, G. T. & Heath, W. R. Transfer of antigen between migrating and lymph node-resident DCs in peripheral T-cell tolerance and immunity. Trends Immunol.25, 655–658 (2004). CASPubMed Google Scholar
Spörri, R. & Reis e Sousa, C. Newly-activated T cells promote maturation of bystander dendritic cells but not IL-12 production. J. Immunol.171, 6406–6413 (2003). PubMed Google Scholar
Wilson, N. S., El-Sukkari, D. & Villadangos, J. A. Dendritic cells constitutively present self antigens in their immature state in vivo and regulate antigen presentation by controlling the rates of MHC class II synthesis and endocytosis. Blood103, 2187–2195 (2004). CASPubMed Google Scholar
Kapsenberg, M. L. Dendritic-cell control of pathogen-driven T-cell polarization. Nature Rev. Immunol.3, 984–993 (2003). CAS Google Scholar
Pulendran, B. Variegation of the immune response with dendritic cells and pathogen recognition receptors. J. Immunol.174, 2457–2465 (2005). CASPubMed Google Scholar
Schulz, O. et al. CD40 triggering of heterodimeric IL-12 p70 production by dendritic cells in vivo requires a microbial priming signal. Immunity13, 453–462 (2000). CASPubMed Google Scholar
Martin-Fontecha, A. et al. Induced recruitment of NK cells to lymph nodes provides IFN-γ for TH1 priming. Nature Immunol.5, 1260–1265 (2004). CAS Google Scholar
Whelan, M. et al. A filarial nematode-secreted product signals dendritic cells to acquire a phenotype that drives development of Th2 cells. J. Immunol.164, 6453–6460 (2000). CASPubMed Google Scholar
MacDonald, A. S., Straw, A. D., Bauman, B. & Pearce, E. J. CD8− dendritic cell activation status plays an integral role in influencing Th2 response development. J. Immunol.167, 1982–1988 (2001). CASPubMed Google Scholar
Jankovic, D., Kullberg, M. C., Caspar, P. & Sher, A. Parasite-induced Th2 polarization is associated with down-regulated dendritic cell responsiveness to Th1 stimuli and a transient delay in T lymphocyte cycling. J. Immunol.173, 2419–2427 (2004). CASPubMed Google Scholar
Amsen, D. et al. Instruction of distinct CD4 T helper cell fates by different notch ligands on antigen-presenting cells. Cell117, 515–526 (2004). CASPubMed Google Scholar
Mahnke, K. & Enk, A. H. Dendritic cells: key cells for the induction of regulatory T cells? Curr. Top. Microbiol. Immunol.293, 133–150 (2005). CASPubMed Google Scholar
Veldhoen, M., Hocking, R. J., Atkins, C. J., Locksley, R. M. & Stockinger, B. TGFβ in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity24, 179–189 (2006). CASPubMed Google Scholar
Liu, Y. J. Dendritic cell subsets and lineages, and their functions in innate and adaptive immunity. Cell106, 259–262 (2001). CASPubMed Google Scholar
Langenkamp, A., Messi, M., Lanzavecchia, A. & Sallusto, F. Kinetics of dendritic cell activation: impact on priming of TH1, TH2 and nonpolarized T cells. Nature Immunol.1, 311–316 (2000). CAS Google Scholar
Kalinski, P., Hilkens, C. M., Wierenga, E. A. & Kapsenberg, M. L. T-cell priming by type-1 and type-2 polarized dendritic cells: the concept of a third signal. Immunol. Today20, 561–567 (1999). CASPubMed Google Scholar
Spörri, R. & Reis e Sousa, C. Inflammatory mediators are insufficient for full dendritic cell activation and promote expansion of CD4+ T cell populations lacking helper function. Nature Immunol.6, 163–170 (2005). Google Scholar
Behrens, G. et al. Helper T cells, dendritic cells and CTL immunity. Immunol. Cell Biol.82, 84–90 (2004). CASPubMed Google Scholar
Steinman, R. M., Hawiger, D. & Nussenzweig, M. C. Tolerogenic dendritic cells. Annu. Rev. Immunol.21, 685–711 (2003). CASPubMed Google Scholar
Scheinecker, C., McHugh, R., Shevach, E. M. & Germain, R. N. Constitutive presentation of a natural tissue autoantigen exclusively by dendritic cells in the draining lymph node. J. Exp. Med.196, 1079–1090 (2002). CASPubMedPubMed Central Google Scholar
Mayerova, D., Parke, E. A., Bursch, L. S., Odumade, O. A. & Hogquist, K. A. Langerhans cells activate naive self-antigen-specific CD8 T cells in the steady state. Immunity21, 391–400 (2004). CASPubMed Google Scholar
Shibaki, A., Sato, A., Vogel, J. C., Miyagawa, F. & Katz, S. I. Induction of GVHD-like skin disease by passively transferred CD8+ T-cell receptor transgenic T cells into keratin 14-ovalbumin transgenic mice. J. Invest. Dermatol.123, 109–115 (2004). CASPubMed Google Scholar
Anderson, M. S. et al. Projection of an immunological self shadow within the thymus by the aire protein. Science298, 1395–1401 (2002). CASPubMed Google Scholar
Anderson, M. S. et al. The cellular mechanism of aire control of T cell tolerance. Immunity23, 227–239 (2005). CASPubMed Google Scholar
Villasenor, J., Benoist, C. & Mathis, D. AIRE and APECED: molecular insights into an autoimmune disease. Immunol. Rev.204, 156–164 (2005). CASPubMed Google Scholar
Jiang, W., Anderson, M. S., Bronson, R., Mathis, D. & Benoist, C. Modifier loci condition autoimmunity provoked by aire deficiency. J. Exp. Med.202, 805–815 (2005). CASPubMedPubMed Central Google Scholar
Piccirillo, C. A. & Shevach, E. M. Naturally-occurring CD4+CD25+ immunoregulatory T cells: central players in the arena of peripheral tolerance. Semin. Immunol.16, 81–88 (2004). CASPubMed Google Scholar
Benvenuti, F. et al. Dendritic cell maturation controls adhesion, synapse formation, and the duration of the interactions with naive T lymphocytes. J. Immunol.172, 292–301 (2004). CASPubMed Google Scholar
Pasare, C. & Medzhitov, R. Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science299, 1033–1036 (2003). CASPubMed Google Scholar
Fazekas de St Groth, B. The evolution of self-tolerance: a new cell arises to meet the challenge of self-reactivity. Immunol. Today19, 448–454 (1998). CASPubMed 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). CASPubMedPubMed Central Google Scholar
Reis e Sousa, C. & Germain, R. N. Analysis of adjuvant function by direct visualization of antigen presentation in vivo: endotoxin promotes accumulation of antigen- bearing dendritic cells in the T cell areas of lymphoid tissue. J. Immunol.162, 6552–6561 (1999). PubMed Google Scholar
Albert, M. L., Jegathesan, M. & Darnell, R. B. Dendritic cell maturation is required for the cross-tolerization of CD8+ T cells. Nature Immunol.2, 1010–1017 (2001). CAS 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). CASPubMedPubMed Central Google Scholar
Perez, V. L. et al. Induction of peripheral T cell tolerance in vivo requires CTLA-4 engagement. Immunity6, 411–417 (1997). CASPubMed Google Scholar
Probst, H. C., McCoy, K., Okazaki, T., Honjo, T. & van den Broek, M. Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4. Nature Immunol.6, 280–286 (2005). CAS Google Scholar
Fujii, S., Liu, K., Smith, C., Bonito, A. J. & Steinman, R. M. The linkage of innate to adaptive immunity via maturing dendritic cells in vivo requires CD40 ligation in addition to antigen presentation and CD80/86 costimulation. J. Exp. Med.199, 1607–1618 (2004). CASPubMedPubMed Central Google Scholar
Kissenpfennig, A. et al. Dynamics and function of Langerhans cells in vivo: dermal dendritic cells colonize lymph node areas distinct from slower migrating Langerhans cells. Immunity22, 643–654 (2005). CASPubMed Google Scholar
Keir, M. E. & Sharpe, A. H. The B7/CD28 costimulatory family in autoimmunity. Immunol. Rev.204, 128–143 (2005). CASPubMed Google Scholar
Watts, T. H. TNF/TNFR family members in costimulation of T cell responses. Annu. Rev. Immunol.23, 23–68 (2005). CASPubMed Google Scholar
Kearney, E. R., Pape, K. A., Loh, D. Y. & Jenkins, M. K. Visualization of peptide-specific T cell immunity and peripheral tolerance induction in vivo. Immunity1, 327–339 (1994). CASPubMed Google Scholar
Zinkernagel, R. M. Localization dose and time of antigens determine immune reactivity. Semin. Immunol.12, 163–171 (2000). CASPubMed Google Scholar
Redmond, W. L. & Sherman, L. A. Peripheral tolerance of CD8 T lymphocytes. Immunity22, 275–284 (2005). CASPubMed Google Scholar
Hugues, S. et al. Distinct T cell dynamics in lymph nodes during the induction of tolerance and immunity. Nature Immunol.5, 1235–1242 (2004). CAS Google Scholar
Shakhar, G. et al. Stable T cell-dendritic cell interactions precede the development of both tolerance and immunity in vivo. Nature Immunol.6, 707–714 (2005). CAS Google Scholar
Hou, W. S. & Van Parijs, L. A. Bcl-2-dependent molecular timer regulates the lifespan and immunogenicity of dendritic cells. Nature Immunol.5, 583–589 (2004). CAS Google Scholar
Lutz, M. B. & Schuler, G. Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity? Trends Immunol.23, 445–449 (2002). CASPubMed Google Scholar
Serbina, N. V., Salazar-Mather, T. P., Biron, C. A., Kuziel, W. A. & Pamer, E. G. TNF/iNOS-producing dendritic cells mediate innate immune defense against bacterial infection. Immunity19, 59–70 (2003). CASPubMed Google Scholar
Fonteneau, J. F. et al. Activation of influenza virus-specific CD4+ and CD8+ T cells: a new role for plasmacytoid dendritic cells in adaptive immunity. Blood101, 3520–3526 (2003). CASPubMed Google Scholar
Salio, M., Palmowski, M. J., Atzberger, A., Hermans, I. F. & Cerundolo, V. CpG-matured murine plasmacytoid dendritic cells are capable of in vivo priming of functional CD8 T cell responses to endogenous but not exogenous antigens. J. Exp. Med.199, 567–579 (2004). CASPubMedPubMed Central Google Scholar
de Heer, H. J. et al. Essential role of lung plasmacytoid dendritic cells in preventing asthmatic reactions to harmless inhaled antigen. J. Exp. Med.200, 89–98 (2004). CASPubMedPubMed Central Google Scholar
Finkelman, F. D., Lees, A., Birnbaum, R., Gause, W. C. & Morris, S. C. Dendritic cells can present antigen in vivo in a tolerogenic or immunogenic fashion. J. Immunol.157, 1406–1414 (1996). CASPubMed Google Scholar
Kurts, C., Cannarile, M., Klebba, I. & Brocker, T. Dendritic cells are sufficient to cross-present self-antigens to CD8 T cells in vivo. J. Immunol.166, 1439–1442 (2001). CASPubMed 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). CASPubMedPubMed 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). CASPubMedPubMed Central Google Scholar
Liu, K. et al. Immune tolerance after delivery of dying cells to dendritic cells in situ. J. Exp. Med.196, 1091–1097 (2002). CASPubMedPubMed Central Google Scholar
Probst, H. C., Lagnel, J., Kollias, G. & van den Broek, M. Inducible transgenic mice reveal resting dendritic cells as potent inducers of CD8+ T cell tolerance. Immunity18, 713–720 (2003). CASPubMed Google Scholar
Albert, M. L. Death-defying immunity: do apoptotic cells influence antigen processing and presentation? Nature Rev. Immunol.4, 223–231 (2004). CAS Google Scholar
Callard, R., George, A. J. & Stark, J. Cytokines, chaos, and complexity. Immunity11, 507–513 (1999). CASPubMed Google Scholar
Huang, F. P. et al. A discrete subpopulation of dendritic cells transports apoptotic intestinal epithelial cells to T cell areas of mesenteric lymph nodes. J. Exp. Med.191, 435–444 (2000). CASPubMedPubMed Central Google Scholar
Heath, W. R. et al. Cross-presentation, dendritic cell subsets, and the generation of immunity to cellular antigens. Immunol. Rev.199, 9–26 (2004). CASPubMed Google Scholar
Manickasingham, S. P. & Reis e Sousa, C. Mature T cell seeks antigen for meaningful relationship in lymph node. Immunology102, 1–11 (2001). Google Scholar
Reis e Sousa, C. et al. In vivo microbial stimulation induces rapid CD40L- independent production of IL-12 by dendritic cells and their re-distribution to T cell areas. J. Exp. Med.186, 1819–1829 (1997). CASPubMed Google Scholar
Asselin-Paturel, C. et al. Type I interferon dependence of plasmacytoid dendritic cell activation and migration. J. Exp. Med.201, 1157–1167 (2005). CASPubMedPubMed Central Google Scholar
Schwartz, R. H. & Mueller, D. L. in Fundamental Immunology (ed. Paul, W. E.) 901–934 (Lippincott Williams & Wilkins, Philadelphia, 2003). Google Scholar
Curtsinger, J. M., Lins, D. C. & Mescher, M. F. Signal 3 determines tolerance versus full activation of naive CD8 T cells: dissociating proliferation and development of effector function. J. Exp. Med.197, 1141–1151 (2003). CASPubMedPubMed Central Google Scholar
Trinchieri, G. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nature Rev. Immunol.3, 133–146 (2003). CAS Google Scholar