The unconventional lifestyle of NKT cells

Nature Reviews Immunology

Volumn 2, Issue 8, 2002, Pages 557-568

  Kronenberg, Mitchell ^a   Gapin, Laurent ^a  

^a LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOKINE; INTERLEUKIN 15; INTERLEUKIN 2; INTERLEUKIN 7; T LYMPHOCYTE RECEPTOR; CD1 ANTIGEN; CD1D ANTIGEN; GAMMA INTERFERON; INTERLEUKIN 4;

ALLERGIC ENCEPHALITIS; ANIMAL CELL; AUTOIMMUNE DISEASE; AUTOIMMUNITY; BONE MARROW; BORRELIA BURGDORFERI; COLITIS; CRYPTOCOCCUS NEOFORMANS; DIABETES MELLITUS; GRAFT REJECTION; HEPATITIS; HEPATITIS B VIRUS; IMMUNE RESPONSE; IMMUNOLOGICAL TOLERANCE; IMMUNOTHERAPY; INFECTION; INFLAMMATION; LEISHMANIA MAJOR; LIVER; LYMPHOID TISSUE; MOUSE; NATURAL KILLER CELL; NONHUMAN; NUDE MOUSE; ORGAN CULTURE; PLASMODIUM FALCIPARUM; PRIORITY JOURNAL; REVIEW; SPLEEN; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; T LYMPHOCYTE SUBPOPULATION; THYMOCYTE; THYMUS; TRYPANOSOMA CRUZI; TUMOR IMMUNITY; ANIMAL; HUMAN; IMMUNOGLOBULIN VARIABLE REGION; IMMUNOLOGY; T LYMPHOCYTE RECEPTOR GENE; TRANSGENIC MOUSE;

ANIMALS; ANTIGENS, CD1; GENES, T-CELL RECEPTOR ALPHA; HUMANS; IMMUNOGLOBULIN VARIABLE REGION; INTERFERON TYPE II; INTERLEUKIN-4; KILLER CELLS, NATURAL; MICE; MICE, TRANSGENIC;

EID: 0036676974     PISSN: 14741733     EISSN: None     Source Type: Journal    
DOI: 10.1038/nri854     Document Type: Review

References (158)

1. Bendefac, A., Rivera, M. N., Park, S. H. & Roark, J. H. Mouse CD1-specific NK1 T cells: development, specificity and function. Annu. Rev. Immunol. 15, 535-562 (1997).
2. Godfrey, D. I., Hammond, K. J., Poulton, L. D., Smyth, M. J. & Baxter, A. G. NKT cells: facts, functions and fallacies. Immunol. Today 21, 573-583 (2000).
3. + T cells in mice and humans. J. Exp. Med. 180, 1097-1106 (1994).
4. + T lymphocytes. Science 268, 863-865 (1995). The first demonstration that Vα14i T cells recognize the non-classical MHC class I molecule CD1d.
5. Kawano, T. et al. CD1d-restricted and TCR-mediated activation of Vα14 NKT cells by glycosylceramides. Science 278, 1626-1629 (1997). This study shows that Vα14iT cells recognize the glycolipid α-galactosyl ceramide (α-GalCer) presented by CD1d.
6. + NKT lymphocytes. J. Immunol. 161, 3271-3281 (1998).
7. 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).
8. 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). The first study of the Vα14i T-cell response ex vivo using CD1d tetramers.
9. Gumperz, J. E. et al. Murine CD1d-restricted T-cell recognition of cellular lipids. Immunity 12, 211-221 (2000).
10. Gui, M., Li, J., Wen, L. J., Hardy, R. R. & Hayakawa, K. TCR β-chain influences but does not solely control autoreactivity of Vα14Jα281 T cells. J. Immunol. 167, 6239-6246 (2001).
11. Brossay, L. et al. CD1d-mediated recognition of an α -galactosylceramide by natural killer T cells is highly conserved through mammalian evolution. J. Exp. Med. 188, 1521-1528 (1998).
12. Spada, F. M., Koezuka, Y. & Porcelli, S. A. CD1d-restricted recognition of synthetic glycolipid antigens by human natural killer T cells. J. Exp. Med. 188, 1529-1534 (1998).
13. + T cells preferentially accumulate in human liver. Eur. J. Immunol. 29, 2406-2413 (1999).
14. Metelitsa, L. S. et al. Human NKT cells mediate antitumor cytotoxicity directly by recognizing target cell CD1d with bound ligand or indirectly by producing IL-2 to activate NK cells. J. Immunol. 167, 3114-3122 (2001).
15. Hammond, K. J. et al. CD1d-restricted NKT cells: an interstrain comparison. J. Immunol. 167, 1164-1173 (2001).
16. Lantz, O., Sharara, L. I., Tilloy, F., Andersson, A. & DiSanto, J. P. Lineage relationships and differentiation of natural killer (NK) T cells: intrathymic selection and interleukin (IL)-4 production in the absence of NKR-P1 and Ly49 molecules. J. Exp. Med. 185, 1396-1401 (1997).
17. 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). A direct demonstration that double-positive thymocytes contain precursors of Vα14i T cells.
18. + CD1d-dependent precursor stage. J. Exp. Med. 195, 835-844 (2002). Evidence that Vα14i T cells are thymus dependent and that expression of NK1.1 can be acquired after export from the thymus.
19. Benlagha, K., Kyin, T., Beavis, A., Teyton, L. & Bendelac, A. A thymic precursor to the NKT-cell lineage. Science 296, 553-555 (2002). Identification of the developmental intermediate stages of Vα14i T cells in the thymus.
20. + T cells. Eur. J. Immunol. 28, 3172-3182 (1998).
21. Eberl, G. et al. Tissue-specific segregation of CD1d-dependent and CD1d-independent NK T cells. J. Immunol. 162, 6410-6419 (1991).
22. + T cells in major histocompatibility complex class-II-deficient mice. J. Exp. Med. 182, 993-1004 (1995).
23. Behar, S. M., Podrebarac, T. A., Roy, C. J., Wang, C. R. & Brenner, M. B. Diverse TCRs recognize murine CD1. J. Immunol. 162, 161-167 (1999).
24. 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).
25. H2-1ike CD1d-reactive T cells that can suppress mixed lymphocyte responses. J. Immunol. 167, 5531-5534 (2001).
26. + T-cell compartments. J. Immunol. 164, 739-745 (2000).
27. Hammond, K. J. et al. NKT cells are phenotypically and functionally diverse. Eur. J. Immunol. 29, 3768-3781 (1999).
28. + T cells. J. Immunol. 164, 2009-2015 (2000).
29. + T cells expressing N K-cell receptors in influenza A virus-infected mice. J. Immunol. 165, 4964-4969 (2000).
30. Arase, H., Saito, T., Phillips, J. H. & Lanier, L. L. Cutting edge: the mouse NK-cell-associated antigen recognized by DX5 monoclonal antibody is CD49b (α2 integrin, very late antigen-2). J. Immunol. 167, 1141-1144 (2001).
31. + T cells in autoimmune diabetes. Nature Immunol. 2, 1117-1125 (2001).
32. Moodycliffe, A. M., Nghiem, D., Clydesdale, G. & Ullrich, S. E. Immune suppression and skin-cancer development: regulation by NKT cells. Nature Immunol. 1, 521-525 (2000).
33. Smiley, S. T., Kaplan, M. H. & Grusby, M. J. Immunoglobulin-E production in the absence of interleukin-4-secreting CD1-dependent cells. Science 275, 977-979 (1997).
34. + T-cell development and early IL-4 production in CD1-deficient mice. Immunity 6, 459-467 (1997).
35. Mendiratta, S. K. et al. CD1d1 mutant mice are deficient in natural T cells that promptly produce IL-4. Immunity 6, 469-477 (1997).
36. Taniguchi, M. & Nakayama, T. Recognition and function of Vα14 NKT cells. Semin. Immunol. 12, 543-550 (2000).
37. + thymocytes selected by MHC class I molecules. Science 263, 1774-1778 (1994).
38. + cells in the liver of mice. J. Exp. Med. 180, 699-704 (1994).
39. + cells J. Immunol. 164, 2412-2418 (2000).
40. + cell lines. Cell. Immunol. 129, 478-493 (1990).
41. + thymocytes. J. Immunol. 146, 1113-1117 (1991).
42. +T cells. J. Exp. Med. 177, 1399-1408 (1993).
43. MacDonald, H. R. CD1d-glycollpid tetramers: a new tool to monitor natural killer T cells in health and disease. J. Exp. Med. 192, 15-19 (2000).
44. + T cells. Int. Immunol. 10, 1491-1499 (1998).
45. + T cells by CD1-expressing cortical thymocytes. J. Exp. Med. 182, 2091-2096 (1995).
46. Robey, E. & Fowlkes, B. J. Selective events in T-cell development. Annu. Rev. Immunol. 12, 675-705 (1994).
47. Alberola-Ila, J., Hogquist, K. A., Swan, K. A. Bevan, M. J. & Perlmutter, R. M. Positive and negative selection invoke distinct signaling pathways. J. Exp. Med. 184, 9-18 (1996).
48. Eberl, G., Lowin-Kropf, B. & MacDonald, H. R. Cutting edge: NKT-cell development is selectively impaired in Fyn-deficient mice. J. Immunol. 163, 4091-4094 (1999).
49. Gadue, P., Morton, N. & Stein, P. L. The Src-family tyrosine kinase Fyn regulates natural killer T-cell development. J. Exp. Med. 190, 1189-1196 (1999).
50. Walunas, T. L., Wang, B., Wang, C. R. & Leiden, J. M. Cutting edge: the Ets1 transcription factor is required for the development of NK T cells in mice. J. Immunol. 164, 2857-2860 (2000).
51. + cell development. J. Immunol. 159, 5931-5935 (1997).
52. Kennedy, M. K. et al. Reversible defects in natural killer and memory CD8 T-cell lineages in interleukin-15-deficient mice. J. Exp. Med. 191, 771-780 (2000).
53. Lodolce, J. P. et al. IL-15 receptor maintains lymphoid homeostasis by supporting lymphocyte homing and proliferation. Immunity 9, 669-676 (1998).
54. Iizuka, K. et al. Requirement for membrane lymphotoxin in natural killer cell development. Proc. Natl Acad. Sci. USA 96, 6336-6340 (1999).
55. Elewaut, D. et al. Membrane lymphotoxin is required for the development of different subpopulations of NK T cells. J. Immunol. 165, 671-679 (2000).
56. + T cells. Eur. J. Immunol. 27, 1576-1579 (1997).
57. + NK-like cells in the thymus. Blood 97, 1765-1775 (2001).
58. Sato, H. et al. Induction of differentiation of pre-NKT cells to mature Vα14 NKT cells by granulocyte-macrophage colony-stimulating factor. Proc. Natl. Acad. Sci. USA 96, 7439-7444 (1999).
59. + cells. J. Immunol. 159, 1174-1181 (1997).
60. 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 done size. Proc. Natl Acad. Sci. USA 98, 12635-12641 (2001).
61. + thymocytes. Variable influence of self-antigens on T-cell receptor Vβ usage. J. Immunol. 148, 1134-1141 (1991).
62. + thymocytes that express the T-cell receptor may have previously expressed CD8. Int. Immunol. 2, 51-56 (1990).
63. Bendelac, A., Hunziker, R. D. & Lantz, O. Increased interleukin-4 and immunoglobulin-E production in transgenic mice overexpressing NK1 T cells. J. Exp. Med. 184, 1285-1293 (1996).
64. 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).
65. Zerrahn, J. et al. Class I MHC molecules on hematopoietic cells can support intrathymic positive selection of T-cell receptor transgenic T cells. Proc. Natl Acad. Sci. USA 96, 11470-11475 (1999).
66. + regulatory T cells induced by an agonist self-peptide. Nature Immunol. 2, 301-306 (2001).
67. + T cells with MHC class I and class II restricted TCRs is induced by agonist self-peptides. Immunity 16, 355-364 (2002).
68. Chiu, Y. H. et al. Multiple defects in antigen presentation and T-cell development by mice expressing cytoplasmic tail-truncated CD1d. Nature Immunol. 3, 55-60 (2002). This study shows that the loading of a natural ligand during intracellular CD1d transport is likely to be important for the selection of Vα14/T cells.
69. + T cells upon antigen expression in the thymus or in the liver. Eur. J. Immunol. 29, 2330-2343 (1999).
70. + T cells in class-I-restricted TCR-transgenic mice. Cell. Immunol. 213, 24-33 (2001).
71. Wack, A., Coles, M., Norton, T., Hostert, A. & Kioussis, D. Early onset of CD8 transgene expression inhibits the transition from DN3 to DP thymocytes. J. Immunol. 165, 1236-1242 (2000).
72. + cells originate from multiple pathways J. Immunol. 162, 3753-3756 (1999).
73. + NKT cells. J. Immunol. 162, 5094-5098 (1999).
74. 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).
75. Mempel, M. et al. Comparison of the T-cell patterns in leprous and cutaneous sarcoid granulomas. Presence of Vα24-invariant natural killer T cells in T-cell-reactive leprosy together with a highly based T-cell receptor Vα repertoire. Am. J. Pathol. 157, 509-523 (2000).
76. Faunce, D. E., Sonoda, K. H. & Stein-Streilein, J. MIP-2 recruits NKT cells to the spleen during tolerance induction J. Immunol. 166, 313-321 (2001).
77. H1 response and host defense in cryptococcal infection J. Immunol. 167, 6525-6532 (2001). This paper, together with related work from this group, shows that Vα14i T cells localize to the lungs in response to MCP1 and are important for the response to Cryptococcus neoformans.
78. + NKT lymphocytes are activated memory cells. Eur. J. Immunol. 30, 1544-1550 (2000).
79. van Der Viet, H. J. et al. Human natural killer T cells acquire a memory-activated phenotype before birth. Blood 95, 2440-2442 (2000).
80. + NKT cells in germ-free mice. Eur. J. Immunol. 30, 620-625 (2000).
81. Ikarashi, Y. et al. Dendritic-cell maturation overrules H-2D-mediated natural killer T (NKT)-cell inhibition. Critical role for B7 in CD1d-dependent NKT-cell interferon-γ production. J. Exp. Med. 194, 1179-1186 (2001).
82. Maeda, M., Lohwasser, S., Yamamura, T. & Takei, F. Regulation of NKT cells by Ly49: analysis of primary NKT cells and generation of NKT-cell line. J. Immunol. 167, 4180-4186 (2001).
83. Exley, M., Porcelli, S., Furman, M., Garcia, J. & Balk, S. CD161 (NKR-P1A) costimulation of CD1d-dependent activation of human T cells expressing invariant Vα24 JαQ T-cell receptor α-chains. J. Exp. Med. 188, 867-876 (1998).
84. Bousso, P. & Kourilsky, P. A clonal view of αβ T-cell responses. Semin. Immunol. 11, 423-431 (1999).
85. Leite-De-Moraes, M. C. et al. Fas/Fas ligand interactions promote activation-induced cell death of NK T lymphocytes. J. Immunol. 165, 4367-4371 (2000).
86. Osman, Y. et al. Activation of hepatic NKT cells and subsequent liver injury following administration of α-galactosylceramide. Eur. J. Immunol. 30, 1919-1928 (2000).
87. Hayakawa, Y. et al. Critical contribution of IFN-γ and NK cells, but not perforin-mediated cytotoxicity, to anti-metastatic effect of α-galactosylceramide. Eur. J. Immunol. 31, 1720-1727 (2001).
88. Ebed, G. & MacDonald, H. R. Rapid death and regeneration of NKT cells in anti-CD3ε- or IL-12-treated mice: a major role for bone marrow in NKT-cell homeostasis. Immunity 9, 345-353 (1998). A demonstration that Vα14i T cells respond quickly then disappear, probably through the activation-induced cell-death process.
89. Hobbs, J. A. et al. Selective loss of natural killer T cells by apoptosis following infection with lymphocytic choriomeningitis virus. J. Virol. 75, 10746-10754 (2001).
90. + T cells. J. Exp. Med. 187, 2109-2114 (1998).
91. + T cells. Eur. J. Immunol. 30, 2488-2496 (2000).
92. Kawano, T. et al. Antitumor cytotoxicity mediated by ligand-activated human Vα24 NKT cells. Cancer Res. 59, 5102-5105 (1999).
93. 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).
94. Ebed, G. & MacDonald, H. R. Selective induction of NK-cell proliferation and cytotoxicity by activated NKT cells. Eur. J. Immunol. 30, 986-992 (2000).
95. H2 phenotype. J. Immunol. 163, 2373-2377 (1999).
96. Nishimura, T. et al. The interface between innate and acquired immunity: glycolipid antigen presentation by CD1d-expressing dendritic cells to NKT cells induces the differentiation of antigen-specific cytotoxic T lymphocytes. Int. Immunol. 12, 987-994 (2000).
97. 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).
98. Nakagawa, R. et al. Antitumor activity of α-galactosylceramide KRN7000, in mice with the melanoma B16 hepatic metastasis and immunohistological study of tumor-infiltrating cells. Oncol. Res. 12, 51-58 (2000).
99. H2 cytokine synthesis. Eur. J. Immunol. 29, 2014-2025 (1999).
100. 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).
101. H2 phenotype using α-GalCer analogues, and shows the importance of this subset in protection against allergic encephalomyelitis.
102. Kadowaki, N. et al. Distinct cytokine profiles of neonatal natural killer T cells after expansion with subsets of dendritic cells. J. Exp. Med. 193, 1221-7226 (2001).
103. + Vα24i T cells, but not double-negative T cells, can produce IL-4. See also Reference 104.
104. Lee, P. T., Benlagha, K., Teyton, L. & Bendelac, A. Distinct functional lineages of human Vα124 natural killer T cells. J. Exp. Med. 195, 637-641 (2002).
105. Hong, S. et al. The natural killer T-cell ligand α -galactosylceramide prevents autoimmune diabetes in non-obese diabetic mice. Nature Med. 7, 1052-1056 (2001).
106. Sharif, S. et al. Activation of natural killer T cells by α-galactosylceramide treatment prevents the onset and recurrence of autoimmune type 1 diabetes. Nature Med. 7, 1057-1062 (2001).
107. Singh, A. K. et al. Natural killer T-cell activation protects mice against experimental autoimmune encephalomyelitis. J. Exp. Med. 194, 1801-1811 (2001).
108. Cui, J. et al. Inhibition of T helper cell type 2 cell differentiation and immunoglobulin-E response by ligand-activated Vα14 natural killer T cells. J. Exp. Med. 190, 783-792 (1999).
109. Schofield, L. et al. CD1d-restricted immunoglobulin G formation to GPI-anchored antigens mediated by NKT cells. Science 283, 225-229 (1999).
110. 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).
111. Romero, J. F., Eberl, G., MacDonald, H. R. & Corradin, G. CD1d-restricted NK T cells are dispensable for specific antibody responses and protective immunity against liver-stage malaria infection in mice. Parasite Immunol. 23, 267-269 (2001).
112. 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).
113. + subsets of intermediate TCR cells, which are constituents of innate immunity. Cell. Immunol. 211, 96-104 (2001).
114. Kakimi, K., Guidotti, L. G., Koezuka, Y. & Chisari, F. V. Natural killer T-cell activation inhibits hepatitis B virus replication in vivo. J. Exp. Med. 192, 921-930 (2000).
115. Baron, J. L. et al. Activation of a nonclassical NKT-cell subset in a transgenic mouse model of hepatitis B virus infection. Immunity 16, 583-594 (2002).
116. Sumida, T. et al. Selective reduction of T cells bearing invariant Vα24JαQ antigen receptor in patients with systemic sclerosis. J. Exp. Med. 182, 1163-1168 (1995).
117. + NKT-cell numbers are decreased in a wide variety of diseases that are characterized by autoreactive tissue damage. Clin. Immunol. 100, 144-148 (2001).
118. Illes, Z. et al. Differential expression of NK T cell Vα24JαQ invariant TCR chain in the lesions of multiple sclerosis and chronic inflammatory demyelinating polyneuropathy. J. Immunol. 164, 4375-4381 (2000).
119. + double-negative regulatory natural killer T cells in autoimmune diseases. Arthritis Rheum. 44, 1127-1138 (2001).
120. Bonish, B. et al. Overexpression of CD1d by keratinocytes in psoriasis and CD1d-dependent IFN-γ production by NKT cells. J. Immunol. 165, 4076-4085 (2000).
121. Nagane, Y., Utsugisawa, K., Obara, D. & Tohgi, H. NKT-associated markers and perforin in hyperplastic thymuses from patients with Myasthenia gravis. Muscle Nerve 24, 1359-1364 (2001).
122. Smyth, M. J. et al. NKT cells - conductors of tumor immunity? Curr. Opin. Immunol. 14, 165-171 (2002).
123. Cui, J. et al. Requirement for Vα14 NKT cells in IL-12-mediated rejection of tumors. Science 278, 1623-1626 (1997). Stimulation of Vα14i T cells by α-GalCer or IL-12 induces tumour rejection.
124. +NKT cells: stimulation of IL-12 production by antigen-presenting cells in the innate immune system. J. Immunol. 163, 93-101 (1999).
125. 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).
126. + T cells and natural killer cells is essential for the antimetastatic effect of α-galactosylceramide. Blood 99, 1259-1266 (2002).
127. Smyth, M. J. et al. Tumor-necrosis factor-related apoptosis-inducing ligand (TRAIL) contributes to interferon-γ-dependent natural killer cell protection from tumor metastasis. J. Exp. Med. 193, 661-670 (2001).
128. Smyth, M. J. et al. Differential tumor surveillance by natural killer (NK) and NKT cells. J. Exp. Med. 191, 661-668 (2000). The first description that Vα14i T cells have an anti-tumour function in the absence of exogenous stimulation with α-GalCer.
129. Terabe, M. et al. NKT-cell-mediated repression of tumor immunosurveillance by IL-13 and the IL-4R-STAT6 pathway. Nature Immunol. 1, 515-520 (2000).
130. + T-cell deficiency and IDDM in NOD/Lt mice. Diabetes 46, 572-582 (1997).
131. 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).
132. + (NKT) thymocytes prevent insulin-dependent diabetes mellitus in nonobese diabetic (NOD)/Lt mice by the influence of interleukin (IL)-4 and/or IL-10. J. Exp. Med. 187, 1047-1056 (1998). This paper shows that the restoration of a normal Vα14i T-cell repertoire by the transfer of Vα14i T cells from non-immune-prone mice into NOD mice confers protection against diabetes.
133. Poulton, L. D. et al. Cytometric and functional analyses of NK- and NKT-cell deficiencies in NOD mice. Int. Immunol. 13, 887-896 (2001).
134. H1 bias of invariant Vα24JaQ T cells in type 1 diabetes. Nature 391, 177-181 (1998). This paper provides evidence that diabetic patients have a reduced number of Vα24i T cells compared with non-diabetic siblings.
135. Kukreja, A. et al. Multiple immuno-regulatory defects in type-1 diabetes. J. Clin. Invest. 109, 131-140 (2002).
136. 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).
137. 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).
138. Jahng, A. W. et al. Activation of natural killer T cells potentiates or prevents experimental autoimmune encephalomyelitis. J. Exp. Med. 194, 1789-1799 (2001).
139. + Vα14 NKT cells play a crucial role in an early stage of protective immunity against infection with Leishmania major. Int. Immunol. 12, 1267-1274 (2000).
140. Porcelli, S. A. & Modlin, R. L. The CD1 system: antigen-presenting molecules for T-cell recognition of lipids and glycolipids. Annu. Rev. Immunol. 17, 297-329 (1999).
141. Behar, S. M., Dascher, C. C., Grusby, M. J., Wang, C. R. & Brenner, M. B. Susceptibility of mice deficient in CD1D or TAP1 to infection with Mycobacterium tuberculosis. J. Exp. Med. 189, 1973-1980 (1999).
142. 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).
143. Dieli, F. et al. Resistance of natural killer T-cell-deficient mice to systemic Shwartzman reaction. J. Exp. Med. 192, 1645-1652 (2000).
144. van der Vliet, H. J. et al. Potent expansion of human natural killer T cells using α-galactosylceramide (KRN7000)-loaded monocyte-derived dendritic cells, cultured in the presence of IL-7 and IL-15. J. Immunol. Methods 247, 61-72 (2001).
145. + T) cells, natural killer cells, and intestinal intraepithelial T cells. J. Exp. Med. 187, 967-972 (1998).
146. + thymocytes associated with intact thymic structure. Proc. Natl Acad. Sci. USA 94, 2472-2477 (1997).
147. Degermann, S., Sollami, G. & Karjalainen, K. Impaired NK1.1 T-cell development in mice transgenic for a T-cell receptor β-chain lacking the large, solvent-exposed Cβ FG loop. J. Exp. Med. 190, 1357-1362 (1999).
148. Saubermann, L. J. et al. Activation of natural killer T cells by α-galactosylceramide in the presence of CD1d provides protection against colitis in mice. Gastroenterology 119, 119-128 (2000).
149. Takeda, K. et al. Critical contribution of liver natural killer T cells to a murine model of hepatitis. Proc. Natl Acad. Sci. USA 97, 5498-5503 (2000).
150. Kaneko, Y. et al. Augmentation of Vα14 NKT-cell-mediated cytotoxicity by interleukin-4 in an autocrine mechanism resulting in the development of concanavalin-A-induced hepatitis. J. Exp. Med. 191, 105-114 (2000).
151. 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).
152. Seino, K. I. et al. Requirement for natural killer T (NKT) cells in the induction of allograft tolerance. Proc. Natl Acad. Sci. USA 98, 2577-2581 (2001).
153. + Vα14 natural killer T cells are essential for acceptance of rat islet xenografts in mice. J. Clin. Invest. 105, 1761-1767 (2000).
154. Ito, K. et al. Involvement of decidual Vα14 NKT cells in abortion. Proc. Natl Acad. Sci. USA 97, 740-744 (2000).
155. 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).
156. H1 response and local host resistance in mice infected with Cryptococcus neoformans. Infect. Immun. 69, 213-220 (2001).
157. + natural killer T cells by α-galactosylceramide in interleukin-18-deficient mice with systemic cryptococcosis. Infect. Immun. 69, 6643-6650 (2001).
158. 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).