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Innate Regulatory iNKT Cells

  • Dalam Ly
  • Terry L. Delovitch
Chapter

Abstract

The complexity of the immune system requires mechanisms, cellular and molecular, that coordinate early innate immune responses to those of late adaptive immune responses. One type of immune cell that is able to mediate this bridge between innate immunity and adaptive immunity is the invariant natural killer T (iNKT) cell. In recent years, much research has been focused on describing the role of iNKT cells in a variety of immune responses, from pathogen clearance, cancer immunity, to autoimmune regulation. In each of these immune conditions, iNKT cells have been shown to play direct or indirect roles in the coordinating immune responses leading to downstream effector activation. In this review, we highlight our current understanding of iNKT cell biology, and provide an overview of iNKT cell antigen specificities and of the role of iNKT cells in regulating immune responses.

Keywords

Natural Killer Cell Cerebral Malaria iNKT Cell Borrelia Burgdorferi Experimental Autoimmune Encephalomyelitis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Janeway, CA. Jr; Medzhitov, R. Innate immune recognition. Annu. Rev. Immunol. 2002, 20: 197–216.PubMedGoogle Scholar
  2. 2.
    Godfrey, DI; MacDonald, HR; Kronenberg, M; Smyth, MJ; Van Kaer, L. NKT cells: what's in a name? Nat. Rev. Immunol. 2004, 4: 231–237.PubMedGoogle Scholar
  3. 3.
    Vincent, MS; Gumperz, JE; Brenner, MB. Understanding the function of CD1-restricted T cells. Nat. Immunol. 2003, 4: 517–523.PubMedGoogle Scholar
  4. 4.
    Yokoyama, WM; Plougastel, BF. Immune functions encoded by the natural killer gene complex. Nat. Rev. Immunol. 2003, 3: 304–316.PubMedGoogle Scholar
  5. 5.
    Bendelac, A; Rivera, MN; Park, SH; Roark, JH. Mouse CD1-specific NK1 T cells: development, specificity, and function. Annu. Rev. Immunol. 1997, 15: 535–562.PubMedGoogle Scholar
  6. 6.
    Godfrey, DI; Kronenberg, M. Going both ways: immune regulation via CD1d-dependent NKT cells. J. Clin. Invest. 2004, 114: 1379–1388.PubMedGoogle Scholar
  7. 7.
    Kronenberg, M. Toward an understanding of NKT cell biology: progress and paradoxes. Annu. Rev. Immunol. 2005, 23: 877–900.PubMedGoogle Scholar
  8. 8.
    Taniguchi, M; Harada, M; Kojo, S; Nakayama, T; Wakao, H. The regulatory role of Valpha14 NKT cells in innate and acquired immune response. Annu. Rev. Immunol. 2003, 21: 483–513.PubMedGoogle Scholar
  9. 9.
    Wilson, SB; Delovitch, TL. Janus-like role of regulatory iNKT cells in autoimmune disease and tumour immunity. Nat. Rev. Immunol. 2003, 3: 211–222.PubMedGoogle Scholar
  10. 10.
    Kawano, T; Cui, J; Koezuka, Y; Toura, I; Kaneko, Y; Motoki, K; Ueno, H; Nakagawa, R; Sato, H; Kondo, E; Koseki, H; Taniguchi, M. CD1d-restricted and TCR-mediated activation of Valpha14 NKT cells by glycosylceramides. Science. 1997, 278: 1626–1629.PubMedGoogle Scholar
  11. 11.
    Brossay, L; Chioda, M; Burdin, N; Koezuka, Y; Casorati, G; Dellabona, P; Kronenberg, M. CD1d-mediated recognition of an alpha-galactosylceramide by natural killer T cells is highly conserved through mammalian evolution. J. Exp. Med. 1998, 188: 1521–1528.PubMedGoogle Scholar
  12. 12.
    Matsuda, JL; Naidenko, OV; Gapin, L; Nakayama, T; Taniguchi, M; Wang, CR; Koezuka, Y; Kronenberg, M. Tracking the response of natural killer T cells to a glycolipid antigen using CD1d tetramers. J. Exp. Med. 2000, 192: 741–754.PubMedGoogle Scholar
  13. 13.
    Sidobre, S; Kronenberg, M. CD1 tetramers: a powerful tool for the analysis of glycolipid-reactive T cells. J. Immunol. Methods 2002, 268: 107–121.PubMedGoogle Scholar
  14. 14.
    Joyce, S; Woods, AS; Yewdell, JW; Bennink, JR; De Silva, AD; Boesteanu, A; Balk, SP; Cotter, RJ; Brutkiewicz, RR. Natural ligand of mouse CD1d1: cellular glycosylphosphatidylinositol. Science 1998, 279: 1541–1544.PubMedGoogle Scholar
  15. 15.
    Giabbai, B; Sidobre, S; Crispin, MD; Sanchez-Ruiz, Y; Bachi, A; Kronenberg, M; Wilson, IA; Degano, M. Crystal structure of mouse CD1d bound to the self ligand phosphatidylcholine: a molecular basis for NKT cell activation. J. Immunol. 2005, 175: 977–984.PubMedGoogle Scholar
  16. 16.
    Brutkiewicz, RR. CD1d ligands: the good, the bad, and the ugly. J. Immunol. 2006, 177: 769–775.PubMedGoogle Scholar
  17. 17.
    Roberts, TJ; Sriram, V; Spence, PM; Gui, M; Hayakawa, K; Bacik, I; Bennink, JR; Yewdell, JW; Brutkiewicz, RR. Recycling CD1d1 molecules present endogenous antigens processed in an endocytic compartment to NKT cells. J. Immunol. 2002, 168: 5409–5414.PubMedGoogle Scholar
  18. 18.
    Kang, SJ; Cresswell, P. Saposins facilitate CD1d-restricted presentation of an exogenous lipid antigen to T cells. Nat. Immunol. 2004, 5: 175–181.PubMedGoogle Scholar
  19. 19.
    Major, AS; Joyce, S; Van Kaer, L. Lipid metabolism, atherogenesis and CD1-restricted antigen presentation. Trends Mol. Med. 2006, 12: 270–278.PubMedGoogle Scholar
  20. 20.
    Zhou, D; Mattner, J; Cantu, C III; Schrantz, N; Yin, N; Gao, Y; Sagiv, Y; Hudspeth, K; Wu, YP; Yamashita, T; Teneberg, S; Wang, D; Proia, RL; Levery, SB; Savage, PB; Teyton, L; Bendelac, A. Lysosomal glycosphingolipid recognition by NKT cells. Science 2004, 306: 1786–1789.PubMedGoogle Scholar
  21. 21.
    Mattner, J; Debord, KL; Ismail, N; Goff, RD; Cantu, C III; Zhou, D; Saint-Mezard, P; Wang, V; Gao, Y; Yin, N; Hoebe, K; Schneewind, O; Walker, D; Beutler, B; Teyton, L; Savage, P.B; Bendelac, A. Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections. Nature 2005, 434: 525–529.PubMedGoogle Scholar
  22. 22.
    Savage, PB; Teyton, L; Bendelac, A. Glycolipids for natural killer T cells. Chem. Soc. Rev. 2006, 35: 771–779.PubMedGoogle Scholar
  23. 23.
    Apostolou, I; Takahama, Y; Belmant, C; Kawano, T; Huerre, M; Marchal, G; Cui, J; Taniguchi, M; Nakauchi, H; Fournie, JJ; Kourilsky, P; Gachelin, G. Murine natural killer T(NKT) cells [correction of natural killer cells] contribute to the granulomatous reaction caused by mycobacterial cell walls. Proc. Natl. Acad. Sci. U. S. A. 1999, 96: 5141–5146.PubMedGoogle Scholar
  24. 24.
    Fischer, K; Scotet, E; Niemeyer, M; Koebernick, H; Zerrahn, J; Maillet, S; Hurwitz, R; Kursar, M; Bonneville, M; Kaufmann, SH; Schaible, UE. Mycobacterial phosphatidylinositol mannoside is a natural antigen for CD1d-restricted T cells. Proc. Natl. Acad. Sci. U. S. A. 2004, 101: 10685–10690.PubMedGoogle Scholar
  25. 25.
    Gilleron, M; Ronet, C; Mempel, M; Monsarrat, B; Gachelin, G; Puzo, G. Acylation state of the phosphatidylinositol mannosides from Mycobacterium bovis bacillus Calmette Guerin and ability to induce granuloma and recruit natural killer T cells. J. Biol. Chem. 2001, 276: 34896–34904.PubMedGoogle Scholar
  26. 26.
    Kinjo, Y; Wu, D; Kim, G, Xing, GW; Poles, MA; Ho, DD; Tsuji, M; Kawahara, K; Wong, CH; Kronenberg, M. Recognition of bacterial glycosphingolipids by natural killer T cells. Nature 2005, 434: 520–525.PubMedGoogle Scholar
  27. 27.
    Sriram, V; Du, W; Gervay-Hague, J; Brutkiewicz, RR. Cell wall glycosphingolipids of Sphingomonas paucimobilis are CD1d-specific ligands for NKT cells. Eur. J. Immunol. 2005, 35: 1692–1701.PubMedGoogle Scholar
  28. 28.
    Kinjo, Y; Tupin, E; Wu, D; Fujio, M; Garcia-Navarro, R; Benhnia, MR; Zajonc, DM; Ben Menachem, G; Ainge, GD; Painter, GF; Khurana, A; Hoebe, K; Behar, SM; Beutler, B; Wilson, IA; Tsuji, M; Sellati, TJ; Wong, CH; Kronenberg, M. Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria. Nat. Immunol. 2006, 7: 978–986.PubMedGoogle Scholar
  29. 29.
    Kumar, H; Belperron, A; Barthold, SW; Bockenstedt, LK. Cutting edge: CD1d deficiency impairs murine host defense against the spirochete, Borrelia burgdorferi. J. Immunol. 2000, 165: 4797–4801.PubMedGoogle Scholar
  30. 30.
    Burdin, N; Brossay, L; Kronenberg, M. Immunization with alpha-galactosylceramide polarizes CD1-reactive NK T cells towards Th2 cytokine synthesis. Eur. J. Immunol. 1999, 29: 2014–2025.PubMedGoogle Scholar
  31. 31.
    Singh, N; Hong, S; Scherer, DC; Serizawa, I; Burdin, N; Kronenberg, M; Koezuka, Y; Van Kaer, L. Cutting edge: activation of NK T cells by CD1d and alpha-galactosylceramide directs conventional T cells to the acquisition of a Th2 phenotype. J. Immunol. 1999, 163: 2373–2377.PubMedGoogle Scholar
  32. 32.
    Parekh, VV; Wilson, MT; Olivares-Villagomez, D; Singh, AK; Wu, L; Wang, CR; Joyce, S; Van Kaer, L. Glycolipid antigen induces long-term natural killer T cell anergy in mice. J. Clin. Invest. 2005, 115: 2572–2583.PubMedGoogle Scholar
  33. 33.
    Uldrich, AP; Crowe, NY; Kyparissoudis, K; Pellicci, DG; Zhan, Y; Lew, AM; Bouillet, P; Strasser, A; Smyth, MJ; Godfrey, DI. NKT cell stimulation with glycolipid antigen in vivo: costimulation-dependent expansion, Bim-dependent contraction, and hyporesponsiveness to further antigenic challenge. J. Immunol. 2005, 175: 3092–3101.PubMedGoogle Scholar
  34. 34.
    Fujii, S; Shimizu, K; Kronenberg, M; Steinman, RM. Prolonged IFN-gamma-producing NKT response induced with alpha-galactosylceramide-loaded DCs. Nat. Immunol. 2002, 3: 867–874.PubMedGoogle Scholar
  35. 35.
    Toura, I; Kawano, T; Akutsu, Y; Nakayama, T; Ochiai, T; Taniguchi, M. Cutting edge: inhibition of experimental tumor metastasis by dendritic cells pulsed with alpha-galactosylceramide. J. Immunol. 1999, 163: 2387–2391.PubMedGoogle Scholar
  36. 36.
    Bezbradica, JS; Stanic, AK; Matsuki, N; Bour-Jordan, H; Bluestone, JA; Thomas, JW; Unutmaz, D; Van Kaer, L; Joyce, S. Distinct roles of dendritic cells and B cells in Va14Ja18 natural T cell activation in vivo. J. Immunol. 2005, 174: 4696–4705.PubMedGoogle Scholar
  37. 37.
    Miyamoto, K; Miyake, S; Yamamura, T. A synthetic glycolipid prevents autoimmune encephalomyelitis by inducing TH2 bias of natural killer T cells. Nature 2001, 413: 531–534.PubMedGoogle Scholar
  38. 38.
    Mizuno, M; Masumura, M; Tomi, C; Chiba, A; Oki, S; Yamamura, T; Miyake, S. Synthetic glycolipid OCH prevents insulitis and diabetes in NOD mice. J. Autoimmun. 2004, 23: 293–300.PubMedGoogle Scholar
  39. 39.
    Oki, S; Chiba, A; Yamamura, T; Miyake, S. The clinical implication and molecular mechanism of preferential IL-4 production by modified glycolipid-stimulated NKT cells. J. Clin. Invest. 2004, 113: 1631–1640.PubMedGoogle Scholar
  40. 40.
    Yu, KO; Im, JS; Molano, A; Dutronc, Y; Illarionov, PA; Forestier, C; Fujiwara, N; Arias, I; Miyake, S; Yamamura, T; Chang, YT; Besra, GS; Porcelli, SA. Modulation of CD1d-restricted NKT cell responses by using N-acyl variants of alpha-galactosylceramides. Proc. Natl. Acad. Sci. U. S. A. 2005, 102: 3383–3388.PubMedGoogle Scholar
  41. 41.
    Schmieg, J; Yang, G; Franck, RW; Tsuji, M. Superior protection against malaria and melanoma metastases by a C-glycoside analogue of the natural killer T cell ligand alpha-Galactosylceramide. J. Exp. Med. 2003, 198: 1631–1641.PubMedGoogle Scholar
  42. 42.
    Fujii, S; Shimizu, K; Hemmi, H; Fukui, M; Bonito, AJ; Chen, G; Franck, RW; Tsuji, M; Steinman, RM. Glycolipid alpha-C-galactosylceramide is a distinct inducer of dendritic cell function during innate and adaptive immune responses of mice. Proc. Natl. Acad. Sci. U. S. A. 2006, 103: 11252–11257.PubMedGoogle Scholar
  43. 43.
    Skold, M; Behar, SM. Role of CD1d-restricted NKT cells in microbial immunity. Infect. Immun. 2003, 71: 5447–5455.PubMedGoogle Scholar
  44. 44.
    Hansen, DS; Schofield, L. Regulation of immunity and pathogenesis in infectious diseases by CD1d-restricted NKT cells. Int. J. Parasitol. 2004, 34: 15–25.PubMedGoogle Scholar
  45. 45.
    Nieuwenhuis, EE; Matsumoto, T; Exley, M; Schleipman, RA; Glickman, J; Bailey, DT; Corazza, N; Colgan, SP; Onderdonk, AB; Blumberg, RS. CD1d-dependent macrophage-mediated clearance of Pseudomonas aeruginosa from lung. Nat. Med. 2002, 8: 588–593.PubMedGoogle Scholar
  46. 46.
    Grubor-Bauk, B; Simmons, A; Mayrhofer, G; Speck, PG. Impaired clearance of herpes simplex virus type 1 from mice lacking CD1d or NKT cells expressing the semivariant V alpha 14-J alpha 281 TCR. J. Immunol. 2003, 170: 1430–1434.PubMedGoogle Scholar
  47. 47.
    Raftery, MJ; Winau, F; Kaufmann, SH; Schaible, UE; Schonrich, G. CD1 antigen presentation by human dendritic cells as a target for herpes simplex virus immune evasion. J. Immunol. 2006, 177: 6207–6214.PubMedGoogle Scholar
  48. 48.
    Yuan, W; Dasgupta, A; Cresswell, P. Herpes simplex virus evades natural killer T cell recognition by suppressing CD1d recycling. Nat. Immunol. 2006, 7: 835–842.PubMedGoogle Scholar
  49. 49.
    van Dommelen, SL; Tabarias, HA; Smyth, MJ; Degli-Esposti, MA. Activation of natural killer (NK) T cells during murine cytomegalovirus infection enhances the antiviral response mediated by NK cells. J. Virol. 2003, 77: 1877–1884.PubMedGoogle Scholar
  50. 50.
    Liu, YJ. IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu. Rev. Immunol. 2005, 23: 275–306.PubMedGoogle Scholar
  51. 51.
    Colonna, M; Trinchieri, G; Liu, J. Plasmacytoid dendritic cells in immunity. Nat. Immunol. 2004, 5: 1219–1226.PubMedGoogle Scholar
  52. 52.
    Marschner, A; Rothenfusser, S; Hornung, V; Prell, D; Krug, A; Kerkmann, M; Wellisch, D; Poeck, H; Greinacher, A; Giese, T; Endres, S; Hartmann, G. CpG ODN enhance antigen-specific NKT cell activation via plasmacytoid dendritic cells. Eur. J. Immunol. 2005, 35: 2347–2357.PubMedGoogle Scholar
  53. 53.
    Montoya, CJ; Jie, HB; Al Harthi, L; Mulder, C; Patino, PJ; Rugeles, MT; Krieg, AM; Landay, AL; Wilson, SB. Activation of plasmacytoid dendritic cells with TLR9 agonists initiates invariant NKT cell-mediated cross-talk with myeloid dendritic cells. J. Immunol. 2006, 177: 1028–1039.PubMedGoogle Scholar
  54. 54.
    Ishikawa, H; Hisaeda, H; Taniguchi, M; Nakayama, T; Sakai, T; Maekawa, Y; Nakano, Y; Zhang, M; Zhang, T; Nishitani, M; Takashima, M; Himeno, K. CD4(+) v(alpha)14 NKT cells play a crucial role in an early stage of protective immunity against infection with Leishmania major. Int. Immunol. 2000, 12: 1267–1274.PubMedGoogle Scholar
  55. 55.
    Gonzalez-Aseguinolaza, G; de Oliveira, C; Tomaska, M; Hong, S; Bruna-Romero, O; Nakayama, T; Taniguchi, M; Bendelac, A; Van Kaer, L; Koezuka, Y; Tsuji, M. alpha-galactosylceramide-activated Valpha 14 natural killer T cells mediate protection against murine malaria. Proc. Natl. Acad. Sci. U. S. A. 2000, 97: 8461–8466.PubMedGoogle Scholar
  56. 56.
    Hansen, DS; Siomos, MA; Buckingham, L; Scalzo, AA; Schofield, L. Regulation of murine cerebral malaria pathogenesis by CD1d-restricted NKT cells and the natural killer complex. Immunity. 2003, 18: 391–402.PubMedGoogle Scholar
  57. 57.
    Cui, J; Shin, T; Kawano, T; Sato, H; Kondo, E; Toura, I; Kaneko, Y; Koseki, H; Kanno, M; Taniguchi, M. Requirement for Valpha14 NKT cells in IL-12-mediated rejection of tumors. Science 1997, 278: 1623–1626.PubMedGoogle Scholar
  58. 58.
    Munz, C; Steinman, RM; Fujii, S. Dendritic cell maturation by innate lymphocytes: coordinated stimulation of innate and adaptive immunity. J. Exp. Med. 2005, 202: 203–207.PubMedGoogle Scholar
  59. 59.
    Seino, K; Motohashi, S; Fujisawa, T; Nakayama, T; Taniguchi, M. Natural killer T cell-mediated antitumor immune responses and their clinical applications. Cancer Sci. 2006, 97: 807–812.PubMedGoogle Scholar
  60. 60.
    Smyth, MJ; Crowe, NY; Hayakawa, Y; Takeda, K; Yagita, H; Godfrey, DI. NKT cells – conductors of tumor immunity? Curr. Opin. Immunol. 2002, 14: 165–171.PubMedGoogle Scholar
  61. 61.
    Hayakawa, Y; Takeda, K; Yagita, H; Kakuta, S; Iwakura, Y; Van Kaer, L; Saiki, I; Okumura, K. Critical contribution of IFN-gamma and NK cells, but not perforin-mediated cytotoxicity, to anti-metastatic effect of alpha-galactosylceramide. Eur. J. Immunol. 2001, 31: 1720–1727.PubMedGoogle Scholar
  62. 62.
    Smyth, MJ; Crowe, NY; Pellicci, DG; Kyparissoudis, K; Kelly, JM; Takeda, K; Yagita, H; Godfrey, DI. Sequential production of interferon-gamma by NK1.1(+) T cells and natural killer cells is essential for the antimetastatic effect of alpha-galactosylceramide. Blood 2002, 99: 1259–1266.PubMedGoogle Scholar
  63. 63.
    Fujii, S; Shimizu, K; Smith, C; Bonifaz, L; Steinman, RM. Activation of natural killer T cells by alpha-galactosylceramide rapidly induces the full maturation of dendritic cells in vivo and thereby acts as an adjuvant for combined CD4 and CD8 T cell immunity to a coadministered protein. J. Exp. Med. 2003, 198: 267–279.PubMedGoogle Scholar
  64. 64.
    Fujii, S; Liu, K; Smith, C; Bonito, AJ; Steinman, RM. 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. 2004, 199: 1607–1618.PubMedGoogle Scholar
  65. 65.
    Smyth, MJ; Thia, KY; Street, SE; Cretney, E; Trapani, JA; Taniguchi, M; Kawano, T; Pelikan, SB; Crowe, NY; Godfrey, DI. Differential tumor surveillance by natural killer (NK) and NKT cells. J. Exp. Med. 2000, 191: 661–668.PubMedGoogle Scholar
  66. 66.
    Crowe, NY; Smyth, MJ; Godfrey, DI. A critical role for natural killer T cells in immunosurveillance of methylcholanthrene-induced sarcomas. J. Exp. Med. 2002, 196: 119–127.PubMedGoogle Scholar
  67. 67.
    Crowe, NY; Coquet, JM; Berzins, SP; Kyparissoudis, K; Keating, R; Pellicci, DG; Hayakawa, Y; Godfrey, DI; Smyth, MJ. Differential antitumor immunity mediated by NKT cell subsets in vivo. J. Exp. Med. 2005, 202: 1279–1288.PubMedGoogle Scholar
  68. 68.
    Kawano, T; Nakayama, T; Kamada, N; Kaneko, Y; Harada, M; Ogura, N; Akutsu, Y; Motohashi, S; Iizasa, T; Endo, H; Fujisawa, T; Shinkai, H; Taniguchi, M. Antitumor cytotoxicity mediated by ligand-activated human V alpha24 NKT cells. Cancer Res. 1999, 59: 5102–5105.PubMedGoogle Scholar
  69. 69.
    Rogers, PR; Matsumoto, A; Naidenko, O; Kronenberg, M; Mikayama, T; Kato, S. Expansion of human Valpha24+ NKT cells by repeated stimulation with KRN7000. J. Immunol. Methods 2004, 285: 197–214.PubMedGoogle Scholar
  70. 70.
    van der Vliet, HJ; Nishi, N; Koezuka, Y; von Blomberg, BM; van den Eertwegh, AJ; Porcelli, SA; Pinedo, HM; Scheper, RJ; Giaccone, G. Potent expansion of human natural killer T cells using alpha-galactosylceramide (KRN7000)-loaded monocyte-derived dendritic cells, cultured in the presence of IL-7 and IL-15. J. Immunol. Methods 2001, 247: 61–72.PubMedGoogle Scholar
  71. 71.
    Giaccone, G; Punt, C.J; Ando, Y; Ruijter, R; Nishi, N; Peters, M; von Blomberg, BM; Scheper, RJ; van der Vliet, HJ; van den Eertwegh, AJ; Roelvink, M; Beijnen, J; Zwierzina, H; Pinedo, HM. A phase I study of the natural killer T-cell ligand alpha-galactosylceramide (KRN7000) in patients with solid tumors. Clin. Cancer Res. 2002, 8: 3702–3709.PubMedGoogle Scholar
  72. 72.
    Nieda, M; Okai, M; Tazbirkova, A; Lin, H; Yamaura, A; Ide, K; Abraham, R; Juji, T; Macfarlane, DJ; Nicol, AJ. Therapeutic activation of Valpha24+Vbeta11+ NKT cells in human subjects results in highly coordinated secondary activation of acquired and innate immunity. Blood 2004, 103: 383–389.PubMedGoogle Scholar
  73. 73.
    Chang, DH; Osman, K; Connolly, J; Kukreja, A; Krasovsky, J; Pack, M; Hutchinson, A; Geller, M; Liu, N; Annable, R; Shay, J; Kirchhoff, K; Nishi, N; Ando, Y; Hayashi, K; Hassoun, H; Steinman, RM; Dhodapkar, MV. Sustained expansion of NKT cells and antigen-specific T cells after injection of alpha-galactosyl-ceramide loaded mature dendritic cells in cancer patients. J. Exp. Med. 2005, 201: 1503–1517.PubMedGoogle Scholar
  74. 74.
    Ishikawa, A; Motohashi, S; Ishikawa, E; Fuchida, H; Higashino, K; Otsuji, M; Iizasa, T; Nakayama, T; Taniguchi, M; Fujisawa, T. A phase I study of alpha-galactosylceramide (KRN7000)-pulsed dendritic cells in patients with advanced and recurrent non-small cell lung cancer. Clin. Cancer Res. 2005, 11: 1910–1917.PubMedGoogle Scholar
  75. 75.
    Motohashi, S; Ishikawa, A; Ishikawa, E; Otsuji, M; Iizasa, T; Hanaoka, H; Shimizu, N; Horiguchi, S; Okamoto, Y; Fujii, S; Taniguchi, M; Fujisawa, T; Nakayama, T. A phase I study of in vitro expanded natural killer T cells in patients with advanced and recurrent non-small cell lung cancer. Clin. Cancer Res. 2006, 12: 6079–6086.PubMedGoogle Scholar
  76. 76.
    Shevach, EM. Regulatory T cells in autoimmmunity. Annu. Rev. Immunol. 2000, 18: 423–449.PubMedGoogle Scholar
  77. 77.
    Sakaguchi, S. Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu. Rev. Immunol. 2004, 22: 531–562.PubMedGoogle Scholar
  78. 78.
    Kronenberg, M; Rudensky, A. Regulation of immunity by self-reactive T cells. Nature. 2005, 435: 598–604.PubMedGoogle Scholar
  79. 79.
    Delovitch, TL; Singh, B. The nonobese diabetic mouse as a model of autoimmune diabetes: immune dysregulation gets the NOD. Immunity. 1997, 7: 727–738.PubMedGoogle Scholar
  80. 80.
    Shoda, LK; Young, DL; Ramanujan, S; Whiting, CC; Atkinson, MA; Bluestone, JA; Eisenbarth, GS; Mathis, D; Rossini, AA; Campbell, SE; Kahn, R; Kreuwel, HT. A comprehensive review of interventions in the NOD mouse and implications for translation. Immunity 2005, 23: 115–126.PubMedGoogle Scholar
  81. 81.
    Van Kaer, L. alpha-Galactosylceramide therapy for autoimmune diseases: prospects and obstacles. Nat. Rev. Immunol. 2005, 5: 31–42.PubMedGoogle Scholar
  82. 82.
    Hammond, KJ; Kronenberg, M. Natural killer T cells: natural or unnatural regulators of autoimmunity? Curr. Opin. Immunol. 2003, 15: 683–689.PubMedGoogle Scholar
  83. 83.
    Lehuen, A; Lantz, O; Beaudoin, L; Laloux, V; Carnaud, C; Bendelac, A; Bach, JF; Monteiro, RC. Overexpression of natural killer T cells protects Valpha14- Jalpha281 transgenic nonobese diabetic mice against diabetes. J. Exp. Med. 1998, 188: 1831–1839.PubMedGoogle Scholar
  84. 84.
    Hammond, KJ; Pellicci, DG; Poulton, LD; Naidenko, OV; Scalzo, AA; Baxter, AG; Godfrey, DI. CD1d-restricted NKT cells: an interstrain comparison. J. Immunol. 2001, 167: 1164–1173.PubMedGoogle Scholar
  85. 85.
    Hong, S; Wilson, MT; Serizawa, I; Wu, L; Singh, N; Naidenko, OV; Miura, T; Haba, T; Scherer, DC; Wei, J; Kronenberg, M; Koezuka, Y; Van Kaer, L. The natural killer T-cell ligand alpha-galactosylceramide prevents autoimmune diabetes in non-obese diabetic mice. Nat. Med. 2001, 7: 1052–1056.PubMedGoogle Scholar
  86. 86.
    Poulton, LD; Smyth, MJ; Hawke, CG; Silveira, P; Shepherd, D; Naidenko, OV; Godfrey, DI; Baxter, A.G. Cytometric and functional analyses of NK and NKT cell deficiencies in NOD mice. Int. Immunol. 2001, 13: 887–896.PubMedGoogle Scholar
  87. 87.
    Sharif, S; Arreaza, GA; Zucker, P; Mi, QS; Sondhi, J; Naidenko, OV; Kronenberg, M; Koezuka, Y; Delovitch, TL; Gombert, JM; Leite-De-Moraes, M; Gouarin, C; Zhu, R; Hameg, A; Nakayama, T; Taniguchi, M; Lepault, F; Lehuen, A; Bach, JF; Herbelin, A. Activation of natural killer T cells by alpha-galactosylceramide treatment prevents the onset and recurrence of autoimmune Type 1 diabetes. Nat. Med. 2001, 7: 1057–1062.PubMedGoogle Scholar
  88. 88.
    Wang, B; Geng, YB; Wang, CR. CD1-restricted NK T cells protect nonobese diabetic mice from developing diabetes. J. Exp. Med. 2001, 194: 313–320.PubMedGoogle Scholar
  89. 89.
    Mi, QS; Ly, D; Zucker, P; McGarry, M; Delovitch, TL. Interleukin-4 but not interleukin-10 protects against spontaneous and recurrent type 1 diabetes by activated CD1d-restricted invariant natural killer T-cells. Diabetes 2004, 53: 1303–1310.PubMedGoogle Scholar
  90. 90.
    Chen, YG; Choisy-Rossi, CM; Holl, TM; Chapman, HD; Besra, GS; Porcelli, SA; Shaffer, DJ; Roopenian, D; Wilson, SB; Serreze, DV. Activated NKT cells inhibit autoimmune diabetes through tolerogenic recruitment of dendritic cells to pancreatic lymph nodes. J. Immunol. 2005, 174: 1196–1204.PubMedGoogle Scholar
  91. 91.
    Novak, J; Beaudoin, L; Griseri, T; Lehuen, A. Inhibition of T cell differentiation into effectors by NKT cells requires cell contacts. J. Immunol. 2005, 174: 1954–1961.PubMedGoogle Scholar
  92. 92.
    Naumov, YN; Bahjat, KS; Gausling, R; Abraham, R; Exley, MA; Koezuka, Y; Balk, SB; Strominger, JL; Clare-Salzer, M; Wilson, SB. Activation of CD1d-restricted T cells protects NOD mice from developing diabetes by regulating dendritic cell subsets. Proc. Natl. Acad. Sci. U. S. A. 2001, 98: 13838–13843.PubMedGoogle Scholar
  93. 93.
    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 beta cells. Immunity 2002, 17: 725–736.PubMedGoogle Scholar
  94. 94.
    Cain, JA; Smith, JA; Ondr, JK; Wang, B; Katz, JD. NKT cells and IFN-gamma establish the regulatory environment for the control of diabetogenic T cells in the nonobese diabetic mouse. J. Immunol. 2006, 176: 1645–1654.PubMedGoogle Scholar
  95. 95.
    Tang, Q; Adams, JY; Tooley, AJ; Bi, M; Fife, BT; Serra, P; Santamaria, P; Locksley, RM; Krummel, MF; Bluestone, JA. Visualizing regulatory T cell control of autoimmune responses in nonobese diabetic mice. Nat. Immunol. 2006, 7: 83–92.PubMedGoogle Scholar
  96. 96.
    Tadokoro, CE; Shakhar, G; Shen, S; Ding, Y; Lino, AC; Maraver, A; Lafaille, JJ; Dustin, ML. Regulatory T cells inhibit stable contacts between CD4+ T cells and dendritic cells in vivo. J. Exp. Med. 2006, 203: 505–511.PubMedGoogle Scholar
  97. 97.
    Griseri, T; Beaudoin, L; Novak, J; Mars, LT; Lepault, F; Liblau, R; Lehuen, A. Invariant NKT cells exacerbate type 1 diabetes induced by CD8 T cells. J. Immunol. 2005, 175: 2091–2101.PubMedGoogle Scholar
  98. 98.
    Wilson, SB; Kent, SC; Patton, KT; Orban, T; Jackson, RA; Exley, M; Porcelli, S; Schatz, DA; Atkinson, MA; Balk, SP; Strominger, JL; Hafler, DA. Extreme Th1 bias of invariant Valpha24JalphaQ T cells in type 1 diabetes. Nature 1998, 391: 177–181.PubMedGoogle Scholar
  99. 99.
    Oikawa, Y; Shimada, A; Yamada, S; Motohashi, Y; Nakagawa, Y; Irie, J; Maruyama, T; Saruta, T. High frequency of valpha24(+) vbeta11(+) T-cells observed in type 1 diabetes. Diabetes Care 2002, 25: 1818–1823.PubMedGoogle Scholar
  100. 100.
    Lee, PT; Putnam, A; Benlagha, K; Teyton, L; Gottlieb, PA; Bendelac, A. Testing the NKT cell hypothesis of human IDDM pathogenesis. J. Clin. Invest. 2002, 110: 793–800.PubMedGoogle Scholar
  101. 101.
    Berzins, SP; Kyparissoudis, K; Pellicci, DG; Hammond, KJ; Sidobre, S; Baxter, A; Smyth, MJ; Kronenberg, M; Godfrey, D.I. Systemic NKT cell deficiency in NOD mice is not detected in peripheral blood: implications for human studies. Immunol. Cell Biol. 2004, 82: 247–252.PubMedGoogle Scholar
  102. 102.
    Kent, SC; Chen, Y; Clemmings, SM; Viglietta, V; Kenyon, NS; Ricordi, C; Hering, B; Hafler, DA. Loss of IL-4 secretion from human type 1a diabetic pancreatic draining lymph node NKT cells. J. Immunol. 2005, 175: 4458–4464.PubMedGoogle Scholar
  103. 103.
    Jahng, AW; Maricic, I; Pedersen, B; Burdin, N; Naidenko, O; Kronenberg, M; Koezuka, Y; Kumar, V. Activation of natural killer T cells potentiates or prevents experimental autoimmune encephalomyelitis. J. Exp. Med. 2001, 194: 1789–1799.PubMedGoogle Scholar
  104. 104.
    Singh, AK; Wilson, MT; Hong, S; Olivares-Villagomez, D; Du, C; Stanic, AK; Joyce, S; Sriram, S; Koezuka, Y; Van Kaer, L. Natural killer T cell activation protects mice against experimental autoimmune encephalomyelitis. J. Exp. Med. 2001, 194: 1801–1811.PubMedGoogle Scholar
  105. 105.
    Furlan, R; Bergami, A; Cantarella, D; Brambilla, E; Taniguchi, M; Dellabona, P; Casorati, G; Martino, G. Activation of invariant NKT cells by alphaGalCer administration protects mice from MOG35–55-induced EAE: critical roles for administration route and IFN-gamma. Eur. J. Immunol. 2003, 33: 1830–1838.PubMedGoogle Scholar
  106. 106.
    Mars, LT; Laloux, V; Goude, K; Desbois, S; Saoudi, A; Van Kaer, L; Lassmann, H; Herbelin, A; Lehuen, A; Liblau, RS. Cutting edge: V alpha 14-J alpha 281 NKT cells naturally regulate experimental autoimmune encephalomyelitis in nonobese diabetic mice. J. Immunol. 2002, 168: 6007–6011.PubMedGoogle Scholar
  107. 107.
    Araki, M; Kondo, T; Gumperz, JE; Brenner, MB; Miyake, S; Yamamura, T. Th2 bias of CD4+ NKT cells derived from multiple sclerosis in remission. Int. Immunol. 2003, 15: 279–288.PubMedGoogle Scholar
  108. 108.
    Major, AS; Singh, RR; Joyce, S; Van Kaer, L. The role of invariant natural killer T cells in lupus and atherogenesis. Immunol. Res. 2006, 34: 49–66.PubMedGoogle Scholar
  109. 109.
    Mieza, MA; Itoh, T; Cui, JQ; Makino, Y; Kawano, T; Tsuchida, K; Koike, T; Shirai, T; Yagita, H; Matsuzawa, A; Koseki, H; Taniguchi, M. Selective reduction of V alpha 14+ NK T cells associated with disease development in autoimmune-prone mice. J. Immunol. 1996, 156: 4035–4040.PubMedGoogle Scholar
  110. 110.
    Oishi, Y; Sumida, T; Sakamoto, A; Kita, Y; Kurasawa, K; Nawata, Y; Takabayashi, K; Takahashi, H; Yoshida, S; Taniguchi, M; Saito, Y; Iwamoto, I. Selective reduction and recovery of invariant Valpha24JalphaQ T cell receptor T cells in correlation with disease activity in patients with systemic lupus erythematosus. J. Rheumatol. 2001, 28: 275–283.PubMedGoogle Scholar
  111. 111.
    Kojo, S; Adachi, Y; Keino, H; Taniguchi, M; Sumida, T. Dysfunction of T cell receptor AV24AJ18+, BV11+ double-negative regulatory natural killer T cells in autoimmune diseases. Arthritis Rheum. 2001, 44: 1127–1138.PubMedGoogle Scholar
  112. 112.
    Yang, JQ; Chun, T; Liu, H; Hong, S; Bui, H; Van Kaer, L; Wang, CR; Singh, RR. CD1d deficiency exacerbates inflammatory dermatitis in MRL-lpr/lpr mice. Eur. J. Immunol. 2004, 34: 1723–1732.PubMedGoogle Scholar
  113. 113.
    Yang, JQ; Saxena, V; Xu, H; Van Kaer, L; Wang, CR; Singh, RR. Repeated alpha-galactosylceramide administration results in expansion of NK T cells and alleviates inflammatory dermatitis in MRL-lpr/lpr mice. J. Immunol. 2003, 171: 4439–4446.PubMedGoogle Scholar
  114. 114.
    Forestier, C; Molano, A; Im, JS; Dutronc, Y; Diamond, B; Davidson, A; Illarionov, PA; Besra, GS; Porcelli, SA. Expansion and hyperactivity of CD1d-restricted NKT cells during the progression of systemic lupus erythematosus in (New Zealand Black x New Zealand White)F1 mice. J. Immunol. 2005, 175: 763–770.PubMedGoogle Scholar
  115. 115.
    Zeng, D; Liu, Y; Sidobre, S; Kronenberg, M; Strober, S. Activation of natural killer T cells in NZB/W mice induces Th1-type immune responses exacerbating lupus. J. Clin. Invest. 2003, 112: 1211–1222.PubMedGoogle Scholar
  116. 116.
    La Cava, A; Van Kaer, L; Fu, DS. CD4+CD25+ Tregs and NKT cells: regulators regulating regulators. Trends Immunol. 2006, 27: 322–327.PubMedGoogle Scholar
  117. 117.
    Roelofs-Haarhuis, K; Wu, X; Gleichmann, E. Oral tolerance to nickel requires CD4+ invariant NKT cells for the infectious spread of tolerance and the induction of specific regulatory T cells. J. Immunol. 2004, 173: 1043–1050.PubMedGoogle Scholar
  118. 118.
    Liu, R; La Cava, A; Bai, XF; Jee, Y; Price, M; Campagnolo, DI; Christadoss, P; Vollmer, TL; Van Kaer, L; Shi, FD. Cooperation of invariant NKT cells and CD4+CD25+ T regulatory cells in the prevention of autoimmune myasthenia. J. Immunol. 2005, 175: 7898–7904.PubMedGoogle Scholar
  119. 119.
    Jiang, S; Game, DS; Davies, D; Lombardi, G; Lechler, RI. Activated CD1d-restricted natural killer T cells secrete IL-2: innate help for CD4+CD25+ regulatory T cells? Eur. J. Immunol. 2005, 35: 1193–1200.PubMedGoogle Scholar
  120. 120.
    Azuma, T; Takahashi, T; Kunisato, A; Kitamura, T; Hirai, H. Human CD4+ CD25+ regulatory T cells suppress NKT cell functions. Cancer Res. 2003, 63: 4516–4520.PubMedGoogle Scholar
  121. 121.
    Nishikawa, H; Kato, T; Tanida, K; Hiasa, A; Tawara, I; Ikeda, H; Ikarashi, Y; Wakasugi, H; Kronenberg, M; Nakayama, T; Taniguchi, M; Kuribayashi, K; Old, LJ; Shiku, H. CD4+ CD25+ T cells responding to serologically defined autoantigens suppress antitumor immune responses. Proc. Natl. Acad. Sci. U. S. A. 2003, 100: 10902–10906.PubMedGoogle Scholar
  122. 122.
    Ly, D; Mi, QS; Hussain, S; Delovitch, TL. Protection from type 1 diabetes by invariant NK T cells requires the activity of CD4+CD25+ regulatory T cells. J. Immunol. 2006, 177: 3695–3704.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Laboratory of Autoimmune Diabetes, Robarts Research Institute; Department of Microbiology and ImmunologyUniversity of Western Ontario; FOCIS Centre for Clinical Immunology and ImmunotherapeuticsLondonCanada

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