Natural killer T cells: An unconventional t-cell subset with diverse effector and regulatory functions

Journal of Investigative Dermatology

Volumn 129, Issue 7, 2009, Pages 1628-1642

  Balato, Anna ^a,c   Unutmaz, Derya ^b   Gaspari, Anthony A ^c  

^a UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^b NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA GALACTOSYLCERAMIDE; CD161 ANTIGEN; CD1D ANTIGEN; CD94 ANTIGEN; GAMMA INTERFERON; INTERLEUKIN 4; T LYMPHOCYTE RECEPTOR ALPHA CHAIN; T LYMPHOCYTE RECEPTOR BETA CHAIN;

ADAPTIVE IMMUNITY; ALLERGIC ASTHMA; ALLERGIC CONJUNCTIVITIS; ALLERGIC ENCEPHALOMYELITIS; ANTIGEN PRESENTATION; ANTIGEN RECOGNITION; ATHEROSCLEROSIS; ATOPIC DERMATITIS; AUTOIMMUNITY; CELL ACTIVATION; CELL DIFFERENTIATION; CELL FUNCTION; DRUG ACTIVITY; ENTERITIS; HUMAN; IMMUNOPATHOGENESIS; INFECTION; INNATE IMMUNITY; INSULIN DEPENDENT DIABETES MELLITUS; MULTIPLE SCLEROSIS; NATURAL KILLER T CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PSORIASIS; REVIEW; RHEUMATOID ARTHRITIS; SKIN ALLERGY; SKIN CANCER; SYSTEMIC LUPUS ERYTHEMATOSUS RASH; TRANSPLANTATION; TUMOR IMMUNITY; ULCERATIVE COLITIS;

HUMANS; IMMUNE SYSTEM; KILLER CELLS, NATURAL; T-LYMPHOCYTE SUBSETS;

EID: 67449116582     PISSN: 0022202X     EISSN: 15231747     Source Type: Journal    
DOI: 10.1038/jid.2009.30     Document Type: Review

References (188)

1. Akbari O, Stock P, DeKruyff RH, Umetsu DT (2003a) Role of regulatory T cells in allergy and asthma. Curr Opin Immunol 15:627-33
2. Akbari O, Stock P, Meyer E, Kronenberg M, Sidobre S, Nakayama T et al. (2003b) Essential role of NKT cells producing IL-4 and IL-T3 in the development of allergeninduced airway hyperreactivity. Nat Med 9:582-8
3. Angenieux C, Salamero J, Fricker D, Cazenave JP, Coud B, Hanau D et al. (2000) Characterization of CD1e, a third type of CD1 molecule expressed in dendritic cells. J Biol Chem 275:37757-64
4. Araki M, Kondo T, Cumperz JE, Brenner MB, Miyake S, Yamamura T (2003) T(h)2 bias of CD4+ NKT cells derived from multiple sclerosis in remission. Int Immunol 15:279-88
5. Askenase PW (2001) Yes T-cells, but three different T-cells (alpha/beta, gamma/delta and NKT-cells), and also B-1 cells mediate contact hypersensitivity. Clin Exp Immunol 125:345-50
6. Askenase PW, Szczepanik M, Itakura A, Kiener C, Campos RA (2004) Extravascular T-cell recruitment requires initiation begun by Va14 NKT cells and B-1 B cells. Trends Immunol 25:441-9
7. Azuma T, Takahashi T, Kunisato A, Kitamura T, Hirai H (2003) Human CD4+ CD25+ regulatory T cells suppress NKT cell functions. Cancer Res 63:4516-20
8. Balk SP, Bleicher PA, Terhorst C (1989) Isolation and characterization of a cDNA and gene coding for a fourth CD1 molecule. Proc Natl Acad Sci USA 86:252-6
9. Beaudoin L, Laloux V, Novak J, Lucas B, Lehuen A (2002) NKT cells inhibit the onset of diabetes by impairing the development of pathogenic T cells specific for pancreatic beta cells. Immunity 17:725-36
10. Belsito DV (1999) Allergic contact dermatitis. In: Fitzpatrick's Dermatology in General Medicine (Freedberg IM, et al., eds). 5th ed. McGraw-Hill: New York, 1447-61
11. Benlagha K, Weiss A, Beavis A, Teyton L, Bendelac A (2000) In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1 d tetramers. J Exp Med 191:1895-903
12. Berzins S, Uldrich A, Pellicci D, Mcnab F, Kayakawa Y, Smyth M et al. (2004) Parallels and distinctions between T and NKT cell development in the thymus. Immunol Cell Biol 82:269-75
13. Bonish B, Jullien D, Dutronc Y, Huang BB, Modlin R, Spada FM et al. (2000) Overexpression of CD1d by keratinocytes in psoriasis and CD1ddependent IFN-gamma production by NK-T cells. J Immunol 165:4076-85
14. Borg NA, Wun KS, Kjer-Nielsen L, Wilce MC, Pellicci DC, Koh R et al. (2007) CD1 d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor. Nature 448:44-9
15. Brigl M, Bry L, Kent SC, Cumperz JE, Brenner MB (2003) Mechanism of CD1d-restricted natural killer T cell activation during microbial infection. Nat Immunol 4:1230-7
16. Brossay L, Brossay L, Chioda M, Burdin N, Koezuka Y, Casorati C et al. (1998) Cd1d-mediated recognition of an alpha-galactosylceramide by natural killer t cells is highly conserved through mammalian evolution. J Exp Med 188:1521-8
17. Brutkiewicz RR (2006) CD1d ligands: the good, the bad, and the ugly. J Immunol-177:769-75
18. Cameron AL, Kirby B, Fei W, Griffiths CE (2002) Natural killer and natural killer-T cells in psoriasis. Arch Dermatol Res 294:363-9
19. Campos RA, Szczepanik M, Itakura A, Akahira-Azuma M, Sidobre S, Kronenberg M et al. (2003) Cutaneous immunization rapidly activates liver invariant Va14 NKT-cells stimulating B-1 B-cells to initiate recruitment for elicitation of contact sensitivity. J Exp Med 198:1785-96
20. Campos RA, Szczepanik M, Lisbonne M, Itakura A, Leite-de-Moraes M, Askenase PW (2006) Invariant NKT cells rapidly activated via immunization with diverse contact antigens collaborate in vitro with B-1 cells to initiate contact sensitivity. J Immunol 177:3686-94
21. Canchis PW, Bhan AK, Landau SB, Yanh L, Balk SP, Blumberg RS (1993) Tissue distribution of the non-polymorphic major histocompatibility complex class I-like molecule, CD1d. Immunology 80:561-5
22. Chen H, Paul WE (1997) Cultured NK1.1+CD4+ T cells produce large amounts of IL-4 and IFN-y upon activation by anti-CD3 or CD1. J Immunol 159:2240-9
23. Chen YH, Chiu NM, Mandai M, Wang N, Wang CR (1997) Impaired NK1 + T cell development and early IL-4 production in CD1-deficient mice. Immunity 6:459-67
24. Chiba A, Kaieda S, Oki S, Yamamura T, Miyake S (2005) The involvement of Va14 NKT cells in the pathogenesis of arthritis in murine models. Arthritis Rheum 52:1941-8
25. Cohn L, Elias JA, Chupp GL (2004) Asthma: mechanisms of disease persistence and progression. Annu Rev Immunol 22:789-815
26. Crowe NY, Coquet JM, Berzins SP, Kyparissoudis K, Keating R, Pellicci DG et al. (2005) Differential antitumor immunity mediated by NKT cell subsets in vivo. J Exp Med 202:1279-88
27. Crowe NY, Uldrich AP, Kyparissoudis K, Hammond KJ, Hayakawa Y, Sidobre S et al. (2003) Glycolipid antigen drives rapid expansion and sustained cytokine production by NKT cells. J Immunol 1 71:4020-7
28. Daynes RA, Spellman CW (1977) Evidence for the generation of suppressor cells by UV radiation. Cell Immunol 31:182-7
29. Dellabona P, Padovan E, Casorati M, Brockhaus M, Lanzavecchia A (1994) An invariant Vα24-JαQ/Vβ11 T cell receptor is expressed in all individuals by clonally expanded CD4-8- T cells. J Exp Med 180:1171 -6
30. Dougan SK, Kaser A, Blumberg RS (2007) CD1 expression on antigenpresenting cells. Curr Top Microbiol Immunol 314:113-41
31. Duarte N, Stenstrom M, Campino S, Bergman ML, Lundholm M, Holmberg D et al. (2004) Prevention of diabetes in nonobese diabetic mice mediated by CD1d-restricted nonclassical NKT cells. J Immunol 173:3112-8
32. Eger KA, Sundrud MS, Motsinger AA, Tseng M, Van Kaer L, Unutmaz D (2006) Human natural killer T cells are heterogeneous in their capacity to reprogram their effector functions. PLoS ONE 1:e50
33. Elkhal A, Pichavant M, He R, Scott J, Meyer E, Goya S et al. (2006) CD1d restricted natural killer T cells are not required for allergic skin inflammation. J Allergy Clin Immunol 118:1363-8
34. Emoto M, Kaufmann S (2003) Liver NKT cells: an account of heterogeneity. Trends Immunol 24:364-9
35. Exley M, Garcia J, Wilson SB, Spada F, Gerdes D, Tahir SMA et al. (2000) CD1d structure and regulation on human thymocytes, peripheral blood T cells, B cells and monocytes. Immunology 100:37-47
36. Falcone M, Facciotti F, Ghidoli N, Monti P, Olivieri S, Zaccagnino L et al. (2004) Up-regulation of CD1 d expression restores the immunoregulatory function of NKT cells and prevents autoimmune diabetes in nonobese diabetic mice. J Immunol 1 72:5908-16
37. Fischer K, Scotet E, Niemeyer M, Koebemick H, Zerrahn J, Maillet S et al. (2004) Mycobacterial phosphatidylinositol mannoside is a natural antigen for CD1d-restricted T cells. Proc Natl Acad Sci USA 101:10685-90
38. Fishelevich R, Malanina A, Luzina I, Atamas S, Smyth MJ, Porcelli SA et al. (2006) Ceramide-dependent regulation of human epidermal keratinocyte CD1d expression during terminal differentiation. J Immunol 176:2590-9
39. Fisher MS, Kripke ML (1977) Systemic alteration induced in mice by ultraviolet light irradiation and its relationship to ultraviolet carcinogenesis. Proc Natl Acad Sci USA 74:1688-92
40. Fisher MS, Kripke ML (1982) Suppressor T lymphocytes control the development of primary skin cancers in UV-irradiated mice. Science 216:1133-4
41. Fujii S, Shimizu K, Klimek V, Geller MD, Nimer SD, Dhodapkar MV (2003) Severe and selective deficiency of interferon-gamma-producing invariant natural killer T cells in patients with myelodysplastic syndromes. Br J Haematol 122:617-22
42. Fukushima A, Sumia T, Fukuda K, Yamaguchi T, Kumagai N, Nishida T et al. (2006) Modulation of murine experimental allergic conjunctivitis by treatment with α-galactosylceramide. Immunol Lett 107:32-40
43. Furlan R, Bergami A, Cantarella D, Brambilla E, Taniguchi M, Dellabona P et al. (2003) 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 33:1830-8
44. Gausling R, Trollmo C, Hafler DA (2001) Decreases in interleukin-4 secretion by invariant CD4(-)CD8(-)V alpha 24J alpha Q T cells in peripheral blood of patients with relapsing-remitting multiple sclerosis. Clin Immunol 98:11-7
45. Gober MD, Fishelevich R, Zhao Y, Unutmaz D, Gaspari AA (2008) Human natural killer T cells infiltrate into the skin at elicitation sites of allergic contact dermatitis. J Invest Dermatol 128:1460-9
46. Godfrey Dl, Hammond KJ, Poulton LD, Smyth MJ, Baxter AG (2000) NKT cells: facts, functions and fallacies. Immunol Today 21:573-83
47. Godfrey Dl, Kronenberg M (2004) Going both ways: immune regulation via CD1d-dependent NKT cells. J Clin Invest 114:1379-88
48. Godfrey DI, MacDonald HR, Kronenberg M, Smyth MJ, VanKaer L (2004) NKT-cells: what's in a name? Nat Rev Immunol 4:231-7
49. Gonzalez-Aseguinolaza G, de Oliveira C, Tomaska M, Hong S, BrunaRomero O, Nakayama T et al. (2000) Alpha-galactosylceramide-activated Valpha 14 natural killer T cells mediate protection against murine malaria. Proc Natl Acad Sci USA 97:8461-6
50. Gonzalez-Aseguinolaza G, Van Kaer L, Bergmann CC, Wilson JM, Schmieg J, Kronenberg M et al. (2002) Natural killer T cell ligand alpha-galactosylceramide enhances protective immunity induced by malaria vaccines. J Exp Med 195:617-24
51. Gregoire C, Chasson L, Luci C, Tomasello E, Geissmann F, Vivier E et al. (2007) The trafficking of natural killer cells. Immunol Rev 220:169-82
52. Gumperz JE, Brenner MB (2001) CD1-specific T cells in microbial immunity. Curr Opin Immunol 13:471-8
53. Gumperz JE, Miyake S, Yamamura T, Brenner MB (2002) Functionally distinct subsets of CD1d-restricted natural killer T cells revealed by CD1d tetramer staining. J Exp Med 195:625-36
54. Hachem P, Lisbonne M, Michel ML, Diem S, Roongapinun S, Lefort J et al. (2005) α-galactosylceramide-induced iNKT cells suppress experimental allergic asthma in sensitized mice: role of IFN-γ. Eur J Immunol 35:2793-802
55. Hammond KJ, Poulton LD, Palmisano LJ, Silveira PA, Godfrey DI, Baxter AG (1998) alpha/beta-T cell receptor (TCR)+CD4-CD8- (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 187:1047-56
56. Hansen DS, Siomos MA, Buckingham L, Scalzo AA, Schofield L (2003) Regulation of murine cerebral malaria pathogenesis by CD1d-restricted NKT cells and the natural killer complex. Immunity 18:391-402
57. Harada M, Seino K, Wakao H, Sakata S, Ishizuka Y, Ito T et al. (2004) Downregulation of the invariant Va14 antigen receptor in NKT cells upon activation. Int Immunol 16:241-7
58. Hayakawa Y, Godfrey DI, Smyth MJ (2004) Alpha-galactosylceramide: potential immunomodulatory activity and future application. Curr Med Chem 11:241-52
59. Hayakawa Y, Takeda K, Yagita H, Kakuta S, Iwakura Y, Van Kaer L et al. (2001) Critical contribution of IFNgamma and NK cells, but notperforinmediated cytotoxicity, to antimetastatic effect of alpha-galactosylceramide. Eur J Immunol 31:1720-7
60. Hellings N, Raus J, Stinissen P (2002) Insights into the immunopathogenesisof multiple sclerosis. Immunol Res 25:27-51
61. Ho L, Urban B, Jones L, Ogg G, Mcmichael A (2004) CD4(-)CD8alphaalpha subset of CD1d-restricted NKT cells controls T cell expansion. J Immunol 172:7350-8
62. Hong SM, Scherer DC, Singh N, Mendiratta SK, Serizawa I, Koezuka Y et al. (1999) Lipid antigen presentation in the immune system: lessons learned from CD1d knockout mice. Immunol Rev 169:31-44
63. Ilhan F, Kandi B, Akbulut H, Turgut D, Cicek D (2007) Atopic dermatitis and Valpha24+ natural killer T cells. Skinmed 6:218-20
64. Illes Z, Kondo T, Newcombe J, Oka N, Tabira T, Yamamura T (2000) Differential expression of NK T cell Vα24JαQ invariant TCR chain in the lesions of multiple sclerosis and chronic inflammatory demyelinating polyneuropathy. I Immunol 164:4375-81
65. Im JS, Tapinos N, Chae GT, lllarionov PA, Besra GS, DeVries GH et al. (2006) Expression of CD1d molecules by human Schwann cells and potential interactions with immunoregulatory invariant NK T cells. J Immunol 177:5226-35
66. Jahng A, Maricic I, Aguilera C, Cardell S, Halder RC, Kumar V (2004) Prevention of autoimmunity by targeting a distinct, noninvariant CD1dreactive T cell population reactive to sulfatide. J Exp Med 199:947-57
67. Johnson TR, Hong S, Van Kaer L, Koezuka Y, Graham BS (2002) NKT cells contribute to expansion of CD8+ T cells and amplification of antiviral immune responses to respiratory syncytial virus. J Virol 76:4294-303
68. Jukes JP, Wood KJ, Jones ND (2007) Natural Killer T Cells: a bridge to tolerance or a pathway to rejection? Transplantation 84:679-81
69. Kawakami K, Kinjo Y, Uezu K, Yara S, Miyagi K, Koguchi Y et al. (2001) Monocyte chemoattractant protein-1 -dependent increase of Valpha14 NKT cells in lungs and their roles in Th1 response and host defense in cryptococcal infection. J Immunol 167:6525-32
70. Kawamura T, Takeda K, Mendiratta SK, Kawamura H, Van Kaer L, Yagita H et al. (1998) Critical role of NK11 T cells in IL-12-induced immune responses in vivo. J Immunol 160:16-9
71. Kawano T, Cui J, Koezuka Y, Toura I, Kaneko Y, Motoki K et al. (1997) CD1drestricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides. Science 278:1626-9
72. Kawano T, Cui J, Koezuka Y, Toura I, Kaneko Y, Sato H et al. (1998) Natural killer-like nonspecific tumor cell lysis mediated by specific ligandactivated Valpha14 NKT cells. Proc Natl Acad Sci USA 95:5690-3
73. Kim HY, Kim HJ, Min HS, Kim S, Park WS, Park SH et al. (2005) NKT cells promote antibody-induced joint inflammation by suppressing transforming growth factor betai production. J Exp Med 201:41-7
74. Kinjo Y, Kronenberg M (2005) Vα14i NKT cells are innate lymphocytes that participate in the immune response to diverse microbes. J Clin Immunol 25:522-33
75. Kinjo Y, Tupin E, Wu D, Fujio M, Garcia-Navarro R, Benhnia MR et al. (2006) Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria. Nat Immunol 7:978-86
76. Kinjo Y, Wu D, Kim G, Xing GW, Poles MA, Ho DD et al. (2005) Recognition of bacterial glycosphingolipids by natural killer T cells. Nature 434:520-5
77. Kitamura H, Iwakabe K, Yahata T, Nishimura S, Ohta A, Ohmi Y et al. (1999) The natural killer T (NKT) cell ligand alpha-galactosylceramide demonstrates its immunopotentiating effect by inducing interleukin (IL)-12 production by dendritic cells and IL-T2 receptor expression on NKT cells. J Exp Med 189:1121-8
78. Kojo S, Adachi Y, Keino H, Taniguchi M, Sumida T (2001) Dysfunction of T cell receptor AV24AJ18+, BV11+double-negative regulatory natural killer T cells in autoimmune diseases. Arthritis Rheum 44:1127-38
79. Kojo S, Tsutsumi A, Goto D, Sumida T (2003) Low expression levels of soluble CD1d gene in patients with rheumatoid arthritis. J Rheumatol 30:2524-8
80. Kronenberg M, Gapin L (2002) The unconventional lifestyle of NKT cells. Nat Rev Immunol 2:557-68
81. Kumagai N, Fukuda K, Fujitsu Y, Yamamoto K, Nishida T (2006) Role of structural cells of the cornea and conjunctiva in the pathogenesis of vernal keratoconjunctivitis. Prog Retin Eye Res 25:165-87
82. Kumar H, Belperron A, Barthold SW, Bockenstedt LK (2000) Cutting edge: CD1d deficiency impairs murine host defense against the spirochete, Borrelia burgdorferi. J Immunol 165:4797-801
83. Laloux V, Beaudoin L, Jeske D, Carnaud C, Lehuen A (2001) NK T cell-induced protection against diabetes in V alpha 144 alpha 281 transgenic nonobese diabetic mice is associated with a Th2 shift circumscribed regionally to the islets and functionally to islet autoantigen. J Immunol 166:3749-56
84. Lee PT, Benlagha K, Teyton L, Bendelac A (2002a) Distinct functional lineages of human V alpha-24 natural killer T cells. J Exp Med 195:637-41
85. Lee PT, Putnam A, Benlagha K, Teyton L, Gottleib PA, Bendelac A (2002b) Testing the NKT cell hypothesis of human IDDM pathogenesis. J Clin Invest 110:793-800
86. Lehuen A, Lantz O, Beaudoin L, Laloux V, Carnaud C, Bendelac A et al. (1998) Overexpression of natural killer T cells protects Valpha14-Jalpha281 transgenic nonobese diabetic mice against diabetes. J Exp Med 188:1831-9
87. Liao YH, Jee SH, Sheu BC, Huang YL, Tseng MP, Hsu SM et al. (2006) Increased expression of the natural killer cell inhibitory receptor CD94/NKG2A and CD158b on circulating and lesional T cells in patients with chronic plaque psoriasis. Br J Dermatol 155:318-24
88. Linsen L, Somers V, Stinissen P (2005) Immunoregulation of autoimmunity by natural killer T cells. Hum Immunol 66:1193-202
89. Linsen L, Thewissen M, Baeten K, Somers V, Geusens P, Raus J et al. (2005) Peripheral blood, but not synovial fluid NKT cells are biased towards a Th1 -like phenotype in rheumatoid arthritis. Arthritis Res Ther 7:493-502
90. Lisbonne M, Diem S, de Castro Keller A, Lefort J, Araujo LM, Hachem P et al. (2003) Cutting edge: invariant Valpha14 NKT cells are required for allergen-induced airway inflammation and hyperreactivity in an experimental asthma model. J Immunol 171:1637-41
91. Liu T, Uemura Y, Suzuki M, Narita Y, Hirata S, Ohyama H et al. (2008) Distinct subsets of human invariant NKT cells differentially regulate T helper responses via dendritic cells. Eur J Immunol 38:1012-23
92. MacDonald HR, Mycko MP (2007) Development and selection of Valpha 14i NKT cells. Curr Top Microbiol Immunol 314:1954212
93. Maddox L, Schwartz DA (2002) The pathophysiology of asthma. Annu Rev Med 53:477-98
94. Maeda T, Keino H, Asahara H, Taniguchi M, Nishioka K, Sumida T (1999) Decreased TCR AV24AJ18+ doublenegative T cells in rheumatoid synovium. Rheumatology (Oxford) 38:186-8
95. Magnan A, Mely L, Prato S, Vervloet D, Romagne F, Camilla C et al. (2000) Relationships between natural T cells, atopy, IgE levels, and IL-4 production. Allergy 55:286-90
96. Mannino DM, Homa DM, Pertowski CA, Ashizawa A, Nixon LL, Johnson CA etal. (1998) Surveillance for asthma: United States, 1960-1995. MMWR CDC Surveill Summ 47:1-27
97. Mars LT, Laloux V, Goude K, Desbois S, Saoudi A, Van Kaer L et al. (2002) Cutting edge: V alpha 144 alpha 281 NKT cells naturally regulate experimental autoimmune encephalomyelitis in nonobese diabetic mice. J Immunol 168:6007-11
98. Matsuda JL, Gapin L, Baron JL, Sidobre S, Stetson DB, Mohrs M et al. (2003) Mouse V alpha 14i natural killer T cells are resistant to cytokine polarization in vivo. Proc Natl Acad Sci USA 100:8395-00
99. Matsuda JL, Naidenko OV, Gapin L, Nakayama T, Taniguchi M, Wang CR et al. (2000) Tracking the response of natural killer T cells to a glycolipid antigen using CD1d tetramers. J Exp Med 192:741-54
100. Mattner J, Debord KL, Ismail N, Goff RD, Cantu C III, Zhou D et al. (2005) Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections. Nature 434:525-9
101. McCarthy C, Shepherd D, Fleire S, Strange VS, Koch M, Illarionov PA et al. (2007) The length of lipids bound to human CD1d molecules modulates the affinity of NKT cell TCR and the threshold of NKT cell activation. I Exp Med 204:1131-44
102. Mclntire JJ, Umetsu SE, Macaubas C, Hoyte EG, Cinnioglu C, Cavalli-Sforza LL et al. (2003) Immunology: hepatitis A virus link to atopic disease. Nature 425:576
103. Mercer JC, Ragin MJ, August A (2005) Natural killer T cells: rapid responders controlling immunity and disease. Int J Biochem Cell Biol 37:1337-43
104. Meyer EH, DeKruyff RH, Umetsu DT (2007) iNKT cells in allergic disease. Curr Top Microbiol Immunol 314:269-91
105. Meyer EH, Goya S, Akbari O, Berry GJ, Savage PB, Kronenberg M etal. (2006) Glycolipid activation of invariant T cell receptor+NK T cells is sufficient to induce airway hyperreactivity independent of conventional CD4+ T cells. Proc Natl Acad Sci USA 103:2782-7
106. Mieza MA, Itoh T, Cui JQ, Makino Y, Kawano T, Tsuchida K et al. (1996) Selective reduction of V alpha 14+ NK T cells associated with disease development in autoimmune-prone mice. J Immunol 156:4035-40
107. Miyake S, Yamamura T (2005) Therapeutic potential of glycolipid ligands for natural killer (NK) T cells in the suppression of autoimmune disease. Curr Drug Targets Immune Endocr Metabol Disord 5:315-22
108. Miyake S, Yamamura T (2007) Therapeutic potential of CD1d-restricted invariant natural killer T cell-based treatment for autoimmune diseases. Int Rev Immunol 26:73-94
109. Miyamoto K, Miyake S, Yamamura T (2001) A synthetic glycolipid prevents autoimmune encephalomyelitis by inducing TH2 bias of natural killer T cells. Nature 413:531-4
110. Moodycliffe AM, Nghiem D, Clydesdale G, Ullrich SE (2000) Immune suppression and skin cancer development: regulation by NKT cells. Nat Immunol 1:521-5
111. Morshed SR, Mannoor K, Halder RC, Kawamura H, Bannai M, Sekikawa H et al. (2002) Tissuespecific expansion of NKT and CD5+ B cells at the onset of autoimmune disease in (NZBxNZW)F1 mice. Eur J Immunol 32:2551-61
112. Nakagawa R, Nagafune I, Tazunoki Y, Ehara H, Tomura H, lijima R et al. (2001) Mechanisms of the antimetastatic effect in the liver and of the hepatocyte injury induced by α-galactosylceramide in mice. J Immunol 166:6578-84
113. Nakai Y, Iwabuchi K, Fujii S, Ishimori N, Dashtsoodol N, Watano K et al. (2004) Natural killer T cells accelerate atherogenesis in mice. Blood 104:2051-9
114. Naumov YN, Bahjat KS, Gausling R, Abraham R, Exley MA, Koezuka Y et al. (2001) Activation of CD1d-restricted T cells protects NOD mice from developing diabetes by regulating dendritic cell subsets. Proc Natl Acad Sci USA 98:1 3838-43
115. Nickoloff BJ, Bonish B, Huang BB, Porcelli S (2000) Characterization of a T cell line bearing natual killer receptors and capable of creating psoriasis in a SCID mouse model system. J Dermatol Sci 24:212-25
116. Nieuwenhuis EE, Matsumoto T, Exley M, Schleipman RA, Glickman J, Bailey DT et al. (2002) CD1d-dependent macrophage-mediated clearance of Pseudomonas aeruginosa from lung. Nat Med 8:588-93
117. Nieuwenhuis EES, Gillessen S, Scheper RJ, Exley MA, Taniguchi M, Balk SP et al. (2005) CD1d and CD1d-restricted iNKT-cells playa pivotal role in contact hypersensitivity. Exp Dermatol 14:250-8
118. Norris S, Doherty DG, Collins C, McEntee G, Traynor O, Hegarty JE et al. (1999) Natural T cells in the human liver: cytotoxic lymphocytes with dual T cell and natural killer cell phenotype and function are phenotypically heterogenous and include Valpha24-JalphaQ and gammadelta T cell receptor bearing cells. Hum Immunol 60:20-31
119. Oki S, Chiba A, Yamamura T, Miyake S (2004) The clinical implication and molecular mechanism of preferential IL-4 production by modified glycolipid-stimulated NKT cells. J Clin Invest 113:1631-40
120. Oki S, Tomi C, Yamamura T, Miyake S (2005) Preferential T(h)2 polarization by OCH is supported by incompetent NKT cell induction of CD40L and following production of inflammatory cytokines by bystander cells in vivo. Int Immunol 17:1619-29
121. Oh K, Kim S, Park SH, Gu H, Roopenian D, Chung DH et al. (2005) Direct regulatory role of NKT cells in allogeneic graft survival is dependent on the quantitative strength of antigenicity. J Immunol 174:2030-6
122. Ohnishi Y, Tsutsumi A, Goto D, Itoh S, Matsumoto I, Taniguchi M et al. (2005) TCR Valpha14 natural killer T cells function as effector T cells in mice with collagen-induced arthritis. Clin Exp Immunol 141:47-53
123. Oishi Y, Sakamoto A, Kurasawa K, Nakajima H, Nakao A, Nakagawa N et al. (2000) CD4-CD8- T cells bearing invariant Vα24JαQ TCR α-chain are decreased in patients with atopic diseases. Clin Exp Immunol 119:404-11
124. Oishi Y, Sumida T, Sakamoto A, Kita Y, Kurasawa K, Nawata Y et al. (2001) 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 28:275-83
125. Ortaldo JR, Young HA, Winkler-Pickett RT, Bere EW, Murphy WJ, Wiltrout RH (2004) Dissociation of NKT stimulation, cytokine induction, and NK activation in vivo by the use of distinct TCR-binding ceramides. J Immunol 172:943-53
126. Ottaviani C, Nasorri F, Bedini C, de Pita O, Girolomoni G, Cavani A (2006) CD56brightCD16(-) NK cells accumulate in psoriatic skin in response to CXCL10 and CCL5 and exacerbate skin inflammation. Eur J Immunol 36:118-28
127. Pal E, Tabira T, Kawano T, Taniguchi M, Miyake S, Yamamura T (2001) Costimulation-dependent modulation of experimental autoimmune encephalomyelitis by ligand stimulation of V alpha 14 NK T cells. J Immunol 166:662-8
128. Parekh VV, Singh AK, Wilson MT, Olivares-Villagomez D, Bezbradica JS, Inazawa H et al. (2004) Quantitative and qualitative differences in the in vivo response of NKT cells to distinct alpha- and beta-anomeric glycolipids. J Immunol 173:3693-706
129. Porcelli S, Yockey CE, Brenner MB, Balk SP (1993) Analysis of T cell antigen receptor (TCR) expression by human peripheral blood CD4-8- alpha/beta T cells demonstrates preferential use of several V beta genes and an invariant TCR alpha chain. J Exp Med 178:1-16
130. Porubsky S, Speak AO, Luckow B, Cerundolo V, Platt FM, Grone HJ (2007) Normal development and function of invariant natural killer T cells in mice with isoglobotrihexosylceramide (iGb3) deficiency. Proc Natl Acad Sci USA 104:5977-82
131. Prell C, Konstantopoulos N, Heinzelmann B, Frankenberger B, Reinhardt D, Schendel DJ et al. (2003) Frequency of Valpha24+CD161+ natural killer T cells and invariant TCRAV24-AJ18 transcripts in atopic and non-atopic individuals. Immunobiology 208:367-80
132. Prussin C, Foster B (1997) TCR V alpha 24 and V beta 11 coexpression defines a human NK1 T cell analog containing a unique Th0 subpopulation. J Immunol 159:5862-70
133. Rivas JM, Ullrich SE (1994) The role of IL-4, IL-TO, and TNF-α in the immune suppression induced by ultraviolet radiation. J Leukoc Biol 56:769-75
134. Sakuishi K, Oki S, Araki M, Porcelli SA, Miyake S, Yamamura T (2007) Invariant NKT cells biased for IL-5 production act as crucial regulators of inflammation. J Immunol 179:3452-62
135. Schmieg J, Yang G, Franck RW, Tsuji M (2003) Superior protection against malaria and melanoma metastases by a c-glycoside analogue of the natural killer T cell ligand alpha-galactosylceramide. J Exp Med 198:1631-41
136. Schmieg J, Yang G, Franck RW, Van Rooijen N, Tsuji M (2005) Glycolipid presentation to natural killer T cells differs in an organ-dependent fashion. Proc Natl Acad Sci USA 102:1127-32
137. Seino K, Fujii S, Harada M, Motohashi S, Nakayama T, Fujisawa T et al. (2005) Valpha14 NKT cell-mediated anti-tumor responses and their clinical application. Springer Semin Immun 27:65-74
138. Seino K, Motohashi S, Fujisawa T, Nakayama T, Taniguchi M (2006) Natural killer T cell-mediated antitumor immune responses and their clinical applications. Cancer Sci 97:807-12
139. Seino K, Taniguchi M (2004) Functional roles of NKT cell in the immune system. Front Biosci 9:2577-87
140. Seino K, Taniguchi M (2005) NKT cell subsets and subtypes. J Exp Med 202:1623-6
141. Shi FD, Flodstrom M, Balasa B, Kim SH, Van Gunst K, Strominger JL et al. (2001) Germ line deletion of the CD1 locus exacerbates diabetes in the NOD mouse. Proc Natl Acad Sci USA 98:6777-82
142. Sidobre S, Naidenko OV, Sim BC, Gascoigne NR, Garcia KC, Kronenberg M (2002) The V alpha 14 NKT cell TCR exhibits high-affinity binding to a glycolipid/CD1d complex. J Immunol 169:1340-8
143. Sieling PA (2000) CD1 restricted T-cells: T-cells with a unique immunological niche. Clin Immunol 96:3-10
144. Singh AK, Wilson MT, Hong S, Olivares-Villagomez D, Du C, Stanic AK et al. (2001) Natural killer T cell activation protects mice against experimental autoimmune encephalomyelitis. J Exp Med 194:1801-11
145. Singh N, Hong S, Scherer DC, Serizawa I, Burdin N, Kronenberg M et al. (1999) Cutting edge: activation of NK T cells byCD1d and α- Galactosylceramide directs conventional T cells to the acquisition of a Th2 phenotype. J Immunol 163:2373-7
146. Skold M, Behar SM (2003) Role of CD Id-restricted NKT cells in microbial immunity. Infect Immun 71:5447-55
147. Small TN, Knowles RW, Keever C, Kernan NA, Collins N, O'Reilly RJ et al. (1987) M241 (CD1) expression on B lymphocytes. J Immunol 138:2864-8
148. Smyth MJ, Cretney E, Takeda K, Wiltrout RH, Sedger LM, Kayagaki N et al. (2001a) Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) contributes to interferon gamma dependent natural killer cell protection from tumor metastasis. J Exp Med 193:661-70
149. Smyth MJ, Crowe NY, Godfrey Dl (2001 b) NK cells and NKT cells collaborate in host protection from methylcholanthrene-induced fibrosarcoma. Int Immunol 13:459-63
150. Smyth MJ, Crowe NY, Hayakawa Y, Takeda K, Yagita H, Godfrey DI (2002a) NKT cells - conductors of tumor immunity? Curr Opin Immunol 14:165-71
151. Smyth MJ, Crowe NY, Pellicci DG, Kyparissoudis K, Kelly JM, Takeda K et al. (2002b) Sequential production of interferon-gamma by NK1.1+ T cells and natural killer cells is essential for the antimetastatic effect of alpha-galactosylceramide. Blood 99:1259-66
152. Smyth MJ, Godfrey DI (2000) NKT cells and tumor immunity: a double-edged sword. Nat Immunol 1:459-60
153. Smyth MJ, Taniguchi M, Street SE (2000a) The anti-tumor activity of IL-T2: mechanisms of innate immunity that are model and dose dependent. J Immunol 165:2665-70
154. Smyth MJ, Thia KY, Street SE, Cretney E, Trapani JA, Taniguchi M et al. (2000b) Differential tumor surveillance by natural killer (NK) and NKT cells. J Exp Med 191:661-8
155. Sonoda KH, Taniguchi M, Stein-Streilein J (2002) Longterm survival of corneal allografts is dependent on intact CD1d- reactive NKT cells. J Immunol 168:2028-34
156. Speak AO, Salio M, Neville DC, Fontaine J, Priestman DA, Platt N et al. (2007) Implications for invariant natural killer T cell ligands due to the restricted presence of isoglobotrihexosylceramide in mammals. Proc Natl Acad Sci USA 104:5971-6
157. Sriram V, Du W, Gervay-Hague J, Brutkiewicz RR (2005) Cell wall glycosphingolipids of Sphingomonas paucimobilis are CD1d-specific ligands for NKT cells. Eur J Immunol 35:1692-701
158. Stein-Streilein J (2003) Invariant NKT-cells as initiators, licensors, and facilitators of the adaptive immune response. J Exp Med 198:1779-83
159. Stetson DB, Mohrs M, Reinhardt RL, Baron JL, Wang ZE, Gapin L et al. (2003) Constitutive cytokine mRNAs mark natural killer (NK) and NK T cells poised for rapid effector function. J Exp Med 198:1069-76
160. Tahir SM, Cheng O, Shaulov A, Koezuka Y, Bubley GJ, Wilson SB et al. (2001) Loss of IFN-gamma production by invariant NK T cells in advanced cancer. J Immunol 167:4046-50
161. Takahashi T, Nakamura K, Chiba S, Kanda Y, Tamaki K, Hirai H (2003) Vα24+ natural killer T cells are markedly decreased in atopic dermatitis patients. Hum Immunol 64:586-92
162. Taniguchi M, Harada M, Kojo S, Nakayama T, Wakao H (2003) The regulatory role of Valpha14NKT cells in innate and acquired immune response. Annu Rev Immunol 21:483-513
163. Terabe M, Swann J, Ambrosino E, Sinha P, Takaku S, Hayakawa Y et al. (2005) A nonclassical non-Valpha14Jalpha18 CD1d-restricted (type II) NKT cell is sufficient for down-regulation of tumor immunosurveillance. J Exp Med 202:1627-33
164. Thyssen JP, Linneberg A, Menné T, Johansen JD (2007) The epidemiology of contact allergy in the general population: prevalence and main findings. Contact Derm 57:287-99
165. Tomura M, Yu WG, Ahn HJ, Yamashita M, Yang YF, Ono S et al. (1999) A novel function of Valpha14+CD4+NKT cells: stimulation of IL-12 production by antigenpresenting cells in the innate immune system. J Immunol 163:93-101
166. Tupin E, Kinjo Y, Kronenberg M (2007) The unique role of natural killer T cells in the response to microorganisms. Nat Rev Microbiol 5:405-17
167. Tupin E, Nicoletti A, Elhage R, Rudling M, Ljunggren H, Hansson G et al. (2004) CD Id-dependent activation of NKT cells aggravates atherosclerosis. J Exp Med 199:41 7422
168. Ullrich SE, Kripke ML (1984) Mechanisms in the suppression of tumor rejection produced in mice by repeated UV irradiation. J Immunol 133:2786-90
169. Umetsu DT, Mclntire JJ, Akbari O, Macaubas C, DeKruyff RH (2002) Asthma: an epidemic of dysregulated immunity. Nat Immunol 3:715420
170. van der Vliet HJ, Moiling JW, von Blomberg BM, Nishi N, Kölgen W, van den Eertwegh AJ et al. (2004) The immunoregulatory role of CD1 d-restricted natural killer T cells in disease. Clin Immunol 112:8423
171. van der Vliet HJ, von Blomberg BM, Nishi N, Reijm M, Voskuyl AE, van Bodegraven AA et al. (2001) Circulating Valpha24+ Vbeta11+ NKT cell numbers are decreased in a wide variety of diseases that are characterized by autoreactive tissue damage. Clin Immunol 100:144-8
172. van Dommelen SLH, Tabarias HA, Smyth MJ, Degli-Esposti MA (2003) Activation of natural killer (NK) T cells during murine cytomegalovirus infection enhances the antiviral response mediated by NK cells. J Virol 77:1877-84
173. Vijayanand P, Seumois G, Pickard C, Powell RM, Angco G, Sammut D et al. (2007) Natural killer T cells in asthma and chronic obstructive pulmonary disease. N Engl J Med 356:1410422
174. Vissers WH, Arndtz CH, Muys L, Van Erp PE, de Jong EM, van de Kerkhof PC (2004) Memory effector (CD45RO+) and cytotoxic (CD8+) T cells appear early in the margin zone of spreading psoriatic lesions in contrast to cells expressing natural killer receptors, which appear late. Br J Dermatol 150:852-9
175. Wang B, Geng YB, Wang CR (2001) CD1-restricted NKT cells protect nonobese diabetic mice from developing diabetes. J Exp Med 194:313420
176. Wilson MT, Johansson C, Olivares-Villagomez D, Singh AK, Stanic AK, Wang CR et al. (2003) The response of natural killer T cells to glycolipid antigens is characterized by surface receptor down-modulation and expansion. Proc Natl Acad Sci USA 100:10913-8
177. Wilson SB, Delovitch TL (2003) Janus-like role of regulatory iNKT cells in autoimmune disease and tumour immunity. Nat Rev Immunol 3:211422
178. Woodland DL, Dutton RW (2003) Heterogeneity of CD4+ and CD8+T cells. Curr OpIn Immunol 15:336-42
179. Wu D, Xing GW, Poles MA, Horowitz A, Kinjo Y, Sullivan B et al. (2005) Bacterial glycolipids and analogs as antigens for CD Id-restricted NKT cells. Proc Natl Acad Sci USA 102:1351-6
180. Yanagisawa K, Seino K, Ishikawa Y, Nozue M, Todoroki T, Fukao K (2002) Impaired proliferative response of V alpha 24 NKT cells from cancer patients against alpha-galactosylceramide. J Immunol 168:6494-9
181. Yang G, Schmieg J, Tsuji M, Franck RW (2004) The C-glycoside analogue of the immunostimulant alpha-galactosylceramide (KRN7000): synthesis and striking enhancement of activity. Angew Chem Int Ed Engl 43:3818422
182. Yang J, Saxena V, Xu H, Van Kaer L, Wang C, Singh RR (2003) Repeated alpha-galactosylceramide administration results in expansion of NK T Cells and alleviates inflammatory dermatitis in MRL-lpr/lpr Mice. J Immunol 171:4439-46
183. Yu KO, Im JS, Molano A, Dutronc Y, Illarionov PA, Forestier C et al. (2005) Modulation of CD Id-restricted NKT cell responses by using N-acyl variants of alpha-galactosylceramides. Proc Natl Acad Sci USA 102:3383-8
184. Zajonc DM, Wilson IA (2007) Architecture of CD1 proteins. Curr Top Microbiol Immunol 314:27-50
185. Zeissig S, Kaser A, Dougan SK, Nieuwenhuis EES, Blumberg RS (2007) Role of NKT cells in the digestive system. III. Role of NKT cells in intestinal immunity. Am J Physiol Gastrointest Liver Physiol 293:1101-5
186. Zeng D, Liu Y, Sidobre S, Kronenberg M, Strober S (2003) Activation of natural killer T cells in NZB/W mice induces Th1-type immune responses exacerbating lupus. J Clin Invest 112:1211-22
187. Zhao Y, Fishelevich R, Petrali JP, Zheng L, Anatolievna MA, Deng A et al. (2008) Activation of keratinocyte protein kinase C zeta in psoriasis plaques. J Invest Dermatol 128:2190-7
188. Zhou D, Mattner J, Cantu C III, Schrantz N, Yin N, Gao Y et al. (2004) Lysosomal glycosphingolipid recognition by NKT cells. Science 306:1786-9