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Understanding the function of CD1-restricted T cells

Nature Immunology volume 4, pages 517–523 (2003)Cite this article

Abstract

CD1 molecules bind foreign lipid antigens as they survey the endosomal compartments of infected antigen-presenting cells. Unlike T cells that recognize CD1-restricted foreign lipids, CD1-restricted T cells that are self-antigen–reactive function as 'auto-effectors' that are rapidly stimulated to carry out helper and effector functions upon interaction with CD1-expressing antigen-presenting cells. The functional distinctions between subsets of CD1-restricted T cells, and the pathways by which these cells both influence the inflammatory and tolerogenic effects of dendritic cells and activate natural killer cells and other lymphocytes, provide insight into how CD1-restricted T cells regulate antimicrobial responses, antitumor immunity and the balance between tolerance and autoimmunity.

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Figure 1: Crystal structure of human CD1b with bound phosphatidyl inositol.
Figure 2: T cell–mediated DC 'instruction'.
Figure 3: Effects of foreign antigen and α-GalCer recognition.

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References

  1. Zeng, Z. et al. Crystal structure of mouse CD1: an MHC-like fold with a large hydrophobic binding groove. Science 277, 339–345 (1997).

    Article  CAS  PubMed  Google Scholar 

  2. Gadola, S.D. et al. Structure of human CD1b with bound ligands at 2.3 Å, a maze for alkyl chains. Nat. Immunol. 3, 721–726 (2002).

    Article  CAS  PubMed  Google Scholar 

  3. Calabi, F., Jarvis, J.M., Martin, L. & Milstein, C. Two classes of CD1 genes. Eur. J. Immunol. 19, 285–292 (1989).

    Article  CAS  PubMed  Google Scholar 

  4. Blumberg, R.S. et al. Expression of a nonpolymorphic MHC class I-like molecule, CD1D, by human intestinal epithelial cells. J. Immunol. 147, 2518–2524 (1991).

    CAS  PubMed  Google Scholar 

  5. Brossay, L. et al. Mouse CD1 is mainly expressed on hemopoietic-derived cells. J. Immunol. 159, 1216–1224 (1997).

    CAS  PubMed  Google Scholar 

  6. Spada, F.M. et al. Low expression level but potent antigen presenting function of CD1d on monocyte lineage cells. Eur. J. Immunol. 30, 3468–3477 (2000).

    Article  CAS  PubMed  Google Scholar 

  7. Martin, L.H., Calabi, F. & Milstein, C. Isolation of CD1 genes: a family of major histocompatibility complex–related differentiation antigens. Proc. Natl. Acad. Sci. USA 83, 9154–9158 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Balk, S.P., Bleicher, P.A. & Terhorst, C. Isolation and expression of cDNA encoding the murine homologues of CD1. J. Immunol. 146, 768–774 (1991).

    CAS  PubMed  Google Scholar 

  9. Sugita, M., Porcelli, S.A. & Brenner, M.B. Assembly and retention of CD1b heavy chains in the endoplasmic reticulum. J. Immunol. 159, 2358–2365 (1997).

    CAS  PubMed  Google Scholar 

  10. Kang, S.J. & Cresswell, P. Calnexin, calreticulin, and ERp57 cooperate in disulfide bond formation in human CD1d heavy chain. J. Biol. Chem. 277, 44838–44844 (2002).

    Article  CAS  PubMed  Google Scholar 

  11. Joyce, S. et al. Natural ligand of mouse CD1d1: cellular glycosylphosphatidylinositol. Science 279, 1541–1544 (1998).

    Article  CAS  PubMed  Google Scholar 

  12. De Silva, A.D. et al. Lipid protein interactions: the assembly of CD1d1 with cellular phospholipids occurs in the endoplasmic reticulum. J. Immunol. 168, 723–733 (2002).

    Article  PubMed  Google Scholar 

  13. Sugita, M. et al. Separate pathways for antigen presentation by CD1 molecules. Immunity 11, 743–752 (1999).

    Article  CAS  PubMed  Google Scholar 

  14. Briken, V., Jackman, R.M., Dasgupta, S., Hoening, S. & Porcelli, S.A. Intracellular trafficking pathway of newly synthesized CD1b molecules. EMBO J. 21, 825–834 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Jackman, R.M. et al. The tyrosine-containing cytoplasmic tail of CD1b is essential for its efficient presentation of bacterial lipid antigens. Immunity 8, 341–351 (1998).

    Article  CAS  PubMed  Google Scholar 

  16. Sugita, M. et al. Failure of trafficking and antigen presentation by CD1 in AP-3–deficient cells. Immunity 16, 697–706 (2002).

    Article  CAS  PubMed  Google Scholar 

  17. Chiu, Y.H. et al. Distinct subsets of CD1d-restricted T cells recognize self-antigens loaded in different cellular compartments. J. Exp. Med. 189, 103–110 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Beckman, E.M. et al. Recognition of a lipid antigen by CD1-restricted αβ+ T cells. Nature 372, 691–694 (1994).

    Article  CAS  PubMed  Google Scholar 

  19. Sieling, P.A. et al. CD1-restricted T cell recognition of microbial lipoglycan antigens. Science 269, 227–230 (1995).

    Article  CAS  PubMed  Google Scholar 

  20. Moody, D.B. et al. Structural requirements for glycolipid antigen recognition by CD1b-restricted T cells. Science 278, 283–286 (1997).

    Article  CAS  PubMed  Google Scholar 

  21. Moody, D.B. et al. CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection. Nature 404, 884–888 (2000).

    Article  CAS  PubMed  Google Scholar 

  22. Grant, E.P. et al. Molecular recognition of lipid antigens by T cell receptors. J. Exp. Med. 189, 195–205 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Grant, E.P. et al. Fine specificity of TCR complementarity-determining region residues and lipid antigen hydrophilic moieties in the recognition of a CD1-lipid complex. J. Immunol. 168, 3933–3940 (2002).

    Article  CAS  PubMed  Google Scholar 

  24. Porcelli, S. et al. Recognition of cluster of differentiation 1 antigens by human CD4−CD8− cytolytic T lymphocytes. Nature 341, 447–450 (1989).

    Article  CAS  PubMed  Google Scholar 

  25. Bendelac, A. et al. CD1 recognition by mouse NK1+ T lymphocytes. Science 268, 863–865 (1995).

    Article  CAS  PubMed  Google Scholar 

  26. Exley, M., Garcia, J., Balk, S.P. & Porcelli, S. Requirements for CD1d recognition by human invariant Vα24+CD4−CD8− T cells. J. Exp. Med. 186, 109–120 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. van Der Vliet, H.J. et al. Human natural killer T cells acquire a memory-activated phenotype before birth. Blood 95, 2440–2442 (2000).

    CAS  PubMed  Google Scholar 

  28. Park, S.H., Benlagha, K., Lee, D., Balish, E. & Bendelac, A. Unaltered phenotype, tissue distribution and function of Vα14+ NKT cells in germ-free mice. Eur. J. Immunol. 30, 620–625 (2000).

    Article  CAS  PubMed  Google Scholar 

  29. Ernst, B., Lee, D.S., Chang, J.M., Sprent, J. & Surh, C.D. The peptide ligands mediating positive selection in the thymus control T cell survival and homeostatic proliferation in the periphery. Immunity 11, 173–181 (1999).

    Article  CAS  PubMed  Google Scholar 

  30. Takeda, S., Rodewald, H.R., Arakawa, H., Bluethmann, H. & Shimizu, T. MHC class II molecules are not required for survival of newly generated CD4+ T cells, but affect their long-term life span. Immunity 5, 217–228 (1996).

    Article  CAS  PubMed  Google Scholar 

  31. Stefanova, I., Dorfman, J.R. & Germain, R.N. Self-recognition promotes the foreign antigen sensitivity of naive T lymphocytes. Nature 420, 429–434 (2002).

    Article  CAS  PubMed  Google Scholar 

  32. Spada, F.M. et al. Self-recognition of CD1 by γ/δ T cells: implications for innate immunity. J. Exp. Med. 191, 937–948 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Shamshiev, A. et al. Self glycolipids as T-cell autoantigens. Eur. J. Immunol. 29, 1667–1675 (1999).

    Article  CAS  PubMed  Google Scholar 

  34. Shamshiev, A. et al. Presentation of the same glycolipid by different CD1 molecules. J. Exp. Med. 195, 1013–1021 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Gumperz, J.E. et al. Murine CD1d-restricted T cell recognition of cellular lipids. Immunity 12, 211–221 (2000).

    Article  CAS  PubMed  Google Scholar 

  36. 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 

  37. Ronet, C. et al. Role of the complementarity-determining region 3 (CDR3) of the TCR β-chains associated with the Vα14 semi-invariant TCR α-chain in the selection of CD4+ NK T Cells. J. Immunol. 166, 1755–1762 (2001).

    Article  CAS  PubMed  Google Scholar 

  38. Matsuda, J.L. et al. Natural killer T cells reactive to a single glycolipid exhibit a highly diverse T cell receptor β repertoire and small clone size. Proc. Natl. Acad. Sci. USA 98, 12636–12641 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Yokoyama, W.M. et al. cDNA cloning of mouse NKR-P1 and genetic linkage with LY-49. Identification of a natural killer cell gene complex on mouse chromosome 6. J. Immunol. 147, 3229–3236 (1991).

    CAS  PubMed  Google Scholar 

  40. Park, S.H. et al. The mouse CD1d-restricted repertoire is dominated by a few autoreactive T cell receptor families. J. Exp. Med. 193, 893–904 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Cardell, S. et al. CD1-restricted CD4+ T cells in major histocompatibility complex class II-deficient mice. J. Exp. Med. 182, 993–1004 (1995).

    Article  CAS  PubMed  Google Scholar 

  42. Exley, M.A. et al. A major fraction of human bone marrow lymphocytes are Th2-like CD1d-reactive T cells that can suppress mixed lymphocyte responses. J. Immunol. 167, 5531–5534 (2001).

    Article  CAS  PubMed  Google Scholar 

  43. Kawano, T. et al. CD1d-restricted and TCR-mediated activation of Vα14 NKT cells by glycosylceramides. Science 278, 1626–1629 (1997).

    Article  CAS  PubMed  Google Scholar 

  44. 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 

  45. 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 

  46. Gumperz, J.E., Miyake, S., Yamamura, T. & Brenner, M.B. Functionally distinct subsets of CD1d-restricted natural killer T cells revealed by CD1d tetramer staining. J. Exp. Med. 195, 625–636 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Lee, P.T., Benlagha, K., Teyton, L. & Bendelac, A. Distinct functional lineages of human Vα24 natural killer T cells. J. Exp. Med. 195, 637–641 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Porcelli, S., Morita, C.T. & Brenner, M.B. CD1b restricts the response of human CD4−8− T lymphocytes to a microbial antigen. Nature 360, 593–597 (1992).

    Article  CAS  PubMed  Google Scholar 

  49. Rosat, J.P. et al. CD1-restricted microbial lipid antigen-specific recognition found in the CD8+ αβ T cell pool. J. Immunol. 162, 366–371 (1999).

    CAS  PubMed  Google Scholar 

  50. Sieling, P.A. et al. Evidence for human CD4+ T cells in the CD1-restricted repertoire: derivation of mycobacteria-reactive T cells from leprosy lesions. J. Immunol. 164, 4790–4796 (2000).

    Article  CAS  PubMed  Google Scholar 

  51. Vincent, M.S. et al. CD1-dependent dendritic cell instruction. Nat. Immunol. 3, 1163–1168 (2002).

    Article  CAS  PubMed  Google Scholar 

  52. Cella, M., Engering, A., Pinet, V., Pieters, J. & Lanzavecchia, A. Inflammatory stimuli induce accumulation of MHC class II complexes on dendritic cells. Nature 388, 782–787 (1997).

    Article  CAS  PubMed  Google Scholar 

  53. Pierre, P. et al. Developmental regulation of MHC class II transport in mouse dendritic cells. Nature 388, 787–792 (1997).

    Article  CAS  PubMed  Google Scholar 

  54. Cao, X. et al. CD1 molecules efficiently present antigen in immature dendritic cells and traffic independently of MHC class II during dendritic cell maturation. J. Immunol. 169, 4770–4777 (2002).

    Article  PubMed  Google Scholar 

  55. 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).

    Article  CAS  PubMed  Google Scholar 

  56. Leslie, D.S. et al. CD1-mediated γ/δ T cell maturation of dendritic cells. J. Exp. Med. 196, 1575–1584 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Kitamura, H. et al. The natural killer T (NKT) cell ligand α-galactosylceramide demonstrates its immunopotentiating effect by inducing interleukin (IL)-12 production by dendritic cells and IL-12 receptor expression on NKT cells. J. Exp. Med. 189, 1121–1128 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Beckman, E.M. et al. CD1c restricts responses of mycobacteria-specific T cells. Evidence for antigen presentation by a second member of the human CD1 family. J. Immunol. 157, 2795–2803 (1996).

    CAS  PubMed  Google Scholar 

  59. Stenger, S. et al. Differential effects of cytolytic T cell subsets on intracellular infection. Science 276, 1684–1687 (1997).

    Article  CAS  PubMed  Google Scholar 

  60. Stenger, S. et al. An antimicrobial activity of cytolytic T cells mediated by granulysin. Science 282, 121–125 (1998).

    Article  CAS  PubMed  Google Scholar 

  61. Kawashima, T. et al. Major CD8 T cell response to live BCG is mediated by CD1 molecules. J. Immunol. in the press

  62. Dascher, C.C. et al. Conservation of a CD1 multigene family in the guinea pig. J. Immunol. 163, 5478–5488 (1999).

    CAS  PubMed  Google Scholar 

  63. Hiromatsu, K. et al. Induction of CD1-restricted immune responses in guinea pigs by immunization with mycobacterial lipid antigens. J. Immunol. 169, 330–339 (2002).

    Article  CAS  PubMed  Google Scholar 

  64. Dascher, C.C. et al. Immunization with a mycobacterial lipid vaccine improves pulmonary pathology in the guinea pig model of tuberculosis. Int. Immunol. in the press.

  65. 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 

  66. Gonzalez-Aseguinolaza, G. et al. α-Galactosylceramide-activated Vα14 natural killer T cells mediate protection against murine malaria. Proc. Natl. Acad. Sci. USA 97, 8461–8466 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Kawakami, K. et al. Activation of Vα14+ natural killer T cells by α-galactosylceramide results in development of Th1 response and local host resistance in mice infected with Cryptococcus neoformans. Infect. Immun. 69, 213–220 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Exley, M.A. et al. CD1d-reactive T-cell activation leads to amelioration of disease caused by diabetogenic encephalomyocarditis virus. J. Leukoc. Biol. 69, 713–718 (2001).

    CAS  PubMed  Google Scholar 

  69. Nieuwenhuis, E.E. et al. CD1d-dependent macrophage-mediated clearance of Pseudomonas aeruginosa from lung. Nat. Med. 8, 588–593 (2002).

    Article  CAS  PubMed  Google Scholar 

  70. Chackerian, A., Alt, J., Perera, V. & Behar, S.M. Activation of NKT cells protects mice from tuberculosis. Infect. Immun. 70, 6302–6309 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Duthie, M.S. & Kahn, S.J. Treatment with α-galactosylceramide before Trypanosoma cruzi infection provides protection or induces failure to thrive. J. Immunol. 168, 5778–5785 (2002).

    Article  CAS  PubMed  Google Scholar 

  72. Johnson, T.R., Hong, S., Van Kaer, L., Koezuka, Y. & Graham, B.S. NK T cells contribute to expansion of CD8+ T cells and amplification of antiviral immune responses to respiratory syncytial virus. J. Virol. 76, 4294–4303 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Schofield, L. et al. CD1d-restricted immunoglobulin G formation to GPI-anchored antigens mediated by NKT cells. Science 283, 225–229 (1999).

    Article  CAS  PubMed  Google Scholar 

  74. Molano, A. et al. Cutting edge: the IgG response to the circumsporozoite protein is MHC class II-dependent and CD1d-independent: exploring the role of GPIs in NK T cell activation and antimalarial responses. J. Immunol. 164, 5005–5009 (2000).

    Article  CAS  PubMed  Google Scholar 

  75. Procopio, D.O. et al. Glycosylphosphatidylinositol-anchored mucin-like glycoproteins from Trypanosoma cruzi bind to CD1d but do not elicit dominant innate or adaptive immune responses via the CD1d/NKT cell pathway. J. Immunol. 169, 3926–3933 (2002).

    Article  CAS  PubMed  Google Scholar 

  76. Apostolou, I. et al. Murine natural killer T (NKT) cells contribute to the granulomatous reaction caused by mycobacterial cell walls. Proc. Natl. Acad. Sci. USA 96, 5141–5146 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Mempel, M. et al. Natural killer T cells restricted by the monomorphic MHC class 1b CD1d1 molecules behave like inflammatory cells. J. Immunol. 168, 365–371 (2002).

    Article  CAS  PubMed  Google Scholar 

  78. Kumar, H., Belperron, A., Barthold, S.W. & Bockenstedt, L.K. Cutting edge: CD1d deficiency impairs murine host defense against the spirochete, Borrelia burgdorferi. J. Immunol. 165, 4797–4801 (2000).

    Article  CAS  PubMed  Google Scholar 

  79. Duthie, M.S. et al. During Trypanosoma cruzi infection CD1d-restricted NK T cells limit parasitemia and augment the antibody response to a glycophosphoinositol-modified surface protein. Infect. Immun. 70, 36–48 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Cui, J. et al. Requirement for Vα14 NKT cells in IL-12–mediated rejection of tumors. Science 278, 1623–1626 (1997).

    Article  CAS  PubMed  Google Scholar 

  81. Toura, I. et al. Cutting edge: inhibition of experimental tumor metastasis by dendritic cells pulsed with α-galactosylceramide. J. Immunol. 163, 2387–2391 (1999).

    CAS  PubMed  Google Scholar 

  82. Fujii, S., Shimizu, K., Kronenberg, M. & Steinman, R.M. Prolonged IFN-γ–producing NKT response induced with α-galactosylceramide-loaded DCs. Nat. Immunol. 3, 867–874 (2002).

    Article  CAS  PubMed  Google Scholar 

  83. Hakomori, S. Glycosylation defining cancer malignancy: new wine in an old bottle. Proc. Natl. Acad. Sci. USA 99, 10231–10233 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Ostrand-Rosenberg, S. et al. Resistance to metastatic disease in STAT6-deficient mice requires hemopoietic and nonhematopoietic cells and is IFN-γ dependent. J. Immunol. 169, 5796–5804 (2002).

    Article  CAS  PubMed  Google Scholar 

  85. Terabe, M. et al. NKT cell-mediated repression of tumor immunosurveillance by IL-13 and the IL-4R–STAT6 pathway. Nat. Immunol. 1, 515–520 (2000).

    Article  CAS  PubMed  Google Scholar 

  86. 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 

  87. Smyth, M.J., Crowe, N.Y. & Godfrey, D.I. NK cells and NKT cells collaborate in host protection from methylcholanthrene-induced fibrosarcoma. Int. Immunol. 13, 459–463 (2001).

    Article  CAS  PubMed  Google Scholar 

  88. 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 

  89. Zheng, Z., Venkatapathy, S., Rao, G. & Harrington, C.A. Expression profiling of B cell chronic lymphocytic leukemia suggests deficient CD1-mediated immunity, polarized cytokine response, altered adhesion and increased intracellular protein transport and processing of leukemic cells. Leukemia 16, 2429–2437 (2002).

    Article  CAS  PubMed  Google Scholar 

  90. Sieling, P.A. et al. Human double-negative T cells in systemic lupus erythematosus provide help for IgG and are restricted by CD1c. J. Immunol. 165, 5338–5344 (2000).

    Article  CAS  PubMed  Google Scholar 

  91. 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 

  92. Singh, A.K. et al. Natural killer T cell activation protects mice against experimental autoimmune encephalomyelitis. J. Exp. Med. 194, 1801–1811 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Jahng, A.W. et al. Activation of natural killer T cells potentiates or prevents experimental autoimmune encephalomyelitis. J. Exp. Med. 194, 1789–1799 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Gombert, J.M. et al. Early quantitative and functional deficiency of NK1+-like thymocytes in the NOD mouse. Eur. J. Immunol. 26, 2989–2998 (1996).

    Article  CAS  PubMed  Google Scholar 

  95. Falcone, M., Yeung, B., Tucker, L., Rodriguez, E. & Sarvetnick, N. A defect in interleukin 12–induced activation and interferon γ secretion of peripheral natural killer T cells in nonobese diabetic mice suggests new pathogenic mechanisms for insulin-dependent diabetes mellitus. J. Exp. Med. 190, 963–972 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Hammond, K.J. et al. CD1d-restricted NKT cells: an interstrain comparison. J. Immunol. 167, 1164–1173 (2001).

    Article  CAS  PubMed  Google Scholar 

  97. Baxter, A.G., Kinder, S.J., Hammond, K.J., Scollay, R. & Godfrey, D.I. Association between αβTCR+CD4−CD8− T-cell deficiency and IDDM in NOD/Lt mice. Diabetes 46, 572–582 (1997).

    Article  CAS  PubMed  Google Scholar 

  98. Lehuen, A. et al. Overexpression of natural killer T cells protects Vα14-Jα281 transgenic nonobese diabetic mice against diabetes. J. Exp. Med. 188, 1831–1839 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Sharif, S. et al. Activation of natural killer T cells by α-galactosylceramide treatment prevents the onset and recurrence of autoimmune type 1 diabetes. Nat. Med. 7, 1057–1062 (2001).

    Article  CAS  PubMed  Google Scholar 

  100. Hong, S. et al. The natural killer T-cell ligand α-galactosylceramide prevents autoimmune diabetes in non-obese diabetic mice. Nat. Med. 7, 1052–1056 (2001).

    Article  CAS  PubMed  Google Scholar 

  101. Naumov, Y.N. et al. Activation of CD1d-restricted T cells protects NOD mice from developing diabetes by regulating dendritic cell subsets. Proc. Natl. Acad. Sci. USA 98, 13838–13843 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Shi, F.D. et al. Germ line deletion of the CD1 locus exacerbates diabetes in the NOD mouse. Proc. Natl. Acad. Sci. USA 98, 6777–6782 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Wang, B., Geng, Y.B. & Wang, C.R. CD1-restricted NK T cells protect nonobese diabetic mice from developing diabetes. J. Exp. Med. 194, 313–320 (2001).

    Article  PubMed  PubMed Central  Google Scholar 

  104. Beaudoin, L., Laloux, V., Novak, J., Lucas, B. & Lehuen, A. NKT cells inhibit the onset of diabetes by impairing the development of pathogenic T cells specific for pancreatic β cells. Immunity 17, 725–736 (2002).

    Article  CAS  PubMed  Google Scholar 

  105. Wilson, S.B. et al. Multiple differences in gene expression in regulatory Vα24JαQ T cells from identical twins discordant for type I diabetes. Proc. Natl. Acad. Sci. USA 97, 7411–7416 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Wilson, S.B. et al. Extreme Th1 bias of invariant Vα24JαQ T cells in type 1 diabetes. Nature 391, 177–181 (1998); erratum Nature 399, 84 (1999).

    Article  CAS  PubMed  Google Scholar 

  107. Lee, P.T. et al. Testing the NKT cell hypothesis of human IDDM pathogenesis. J. Clin. Invest. 110, 793–800 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Sonoda, K.H., Exley, M., Snapper, S., Balk, S.P. & Stein-Streilein, J. CD1-reactive natural killer T cells are required for development of systemic tolerance through an immune-privileged site. J. Exp. Med. 190, 1215–1226 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Sonoda, K.H. & Stein-Streilein, J. CD1d on antigen-transporting APC and splenic marginal zone B cells promotes NKT cell-dependent tolerance. Eur. J. Immunol. 32, 848–857 (2002).

    Article  CAS  PubMed  Google Scholar 

  110. Sonoda, K.H. et al. NK T cell-derived IL-10 is essential for the differentiation of antigen-specific T regulatory cells in systemic tolerance. J. Immunol. 166, 42–50 (2001).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank C. Dascher for help with figures. This work was supported by the Arthritis Foundation (M.S.V.), the Charles A. King Trust of the Medical Foundation (J.E.G.) and grants R21AR48037 (M.S.V.) and R37AI29873 (M.B.B.) from the US National Institutes of Health.

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  1. Michael S Vincent and Jenny E Gumperz: These authors contributed equally to this work.

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  1. Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, One Jimmy Fund Way, Boston, 02115, Massachusetts, USA

    Michael S Vincent, Jenny E Gumperz & Michael B Brenner

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Vincent, M., Gumperz, J. & Brenner, M. Understanding the function of CD1-restricted T cells. Nat Immunol 4, 517–523 (2003). https://doi.org/10.1038/ni0603-517

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