Immunosuppressive roles of natural killer T (NKT) cells in the skin

Journal of Leukocyte Biology

Volumn 96, Issue 1, 2014, Pages 49-54

  McKee, Sara J ^a   Mattarollo, Stephen R ^a   Leggatt, Graham R ^a  

^a UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

Glycolipids; Nonmelanoma skin cancer; Transplantation; Ultraviolet radiation

Indexed keywords

CANCER GRAFT; CELL POPULATION; EFFECTOR CELL; EPIDERMIS HYPERPLASIA; GRAFT REJECTION; HUMAN; IMMUNE RESPONSE; IMMUNE SYSTEM; IMMUNOSUPPRESSIVE TREATMENT; LIGHT DAMAGE; NATURAL KILLER T CELL; NON MELANOMA SKIN CANCER; NONHUMAN; ONCOGENE; PRIORITY JOURNAL; RADIATION EXPOSURE; REVIEW; SKIN; SKIN ALLERGY; SKIN CANCER; SKIN GRAFT; SKIN TRANSPLANTATION; SUPPRESSOR CELL; TUMOR IMMUNITY; ULTRAVIOLET RADIATION;

GLYCOLIPIDS; NONMELANOMA SKIN CANCER; TRANSPLANTATION; ULTRAVIOLET RADIATION;

ANIMALS; IMMUNE TOLERANCE; NATURAL KILLER T-CELLS; SKIN; SKIN DISEASES;

EID: 84903531447     PISSN: 07415400     EISSN: 19383673     Source Type: Journal    
DOI: 10.1189/jlb.4RU0114-001R     Document Type: Review

References (86)

1. Bendelac, A., Savage, P. B., Teyton, L. (2007) The biology of NKT cells. Annu. Rev. Immunol. 25, 297-336.
2. Gerlini, G., Hefti, H. P., Kleinhans, M., Nickoloff, B. J., Burg, G., Nestle, F. O. (2001) Cd1d is expressed on dermal dendritic cells and monocytederived dendritic cells. J. Invest. Dermatol. 117, 576-582.
3. Bonish, B., Jullien, D., Dutronc, Y., Huang, B. B., Modlin, R., Spada, F. M., Porcelli, S. A., Nickoloff, B. J. (2000) Overexpression of CD1d by keratinocytes in psoriasis and CD1d-dependent IFN-γ production by NK-T cells. J. Immunol. 165, 4076-4085.
4. Ronger-Savle, S., Valladeau, J., Claudy, A., Schmitt, D., Peguet-Navarro, J., Dezutter-Dambuyant, C., Thomas, L., Jullien, D. (2005) TGFβ inhibits CD1d expression on dendritic cells. J. Invest. Dermatol. 124, 116-118.
5. Godfrey, D. I., Rossjohn, J. (2011) New ways to turn on NKT cells. J. Exp. Med. 208, 1121-1125.
6. Godfrey, D. I., Stankovic, S., Baxter, A. G. (2010) Raising the NKT cell family. Nat. Immunol. 11, 197-206.
7. Eberl, G., Lees, R., Smiley, S. T., Taniguchi, M., Grusby, M. J., MacDonald, H. R. (1999) Tissue-specific segregation of CD1d-dependent and CD1dindependent NK T cells. J. Immunol. 162, 6410-6419.
8. Godfrey, D. I., Hammond, K. J., Poulton, L. D., Smyth, M. J., Baxter, A. G. (2000) NKT cells: facts, functions and fallacies. Immunol. Today 21, 573-583.
9. Doherty, D. G., Norris, S., Madrigal-Estebas, L., McEntee, G., Traynor, O., Hegarty, J. E., O'Farrelly, C. (1999) The human liver contains multiple populations of NK cells, T cells, and CD3+CD56+ natural T cells with distinct cytotoxic activities and Th1, Th2, and Th0 cytokine secretion patterns. J. Immunol. 163, 2314-2321.
10. Gober, M. D., Fishelevich, R., Zhao, Y., Unutmaz, D., Gaspari, A. A. (2008) Human natural killer T cells infiltrate into the skin at elicitation sites of allergic contact dermatitis. J. Invest. Dermatol. 128, 1460-1469.
11. Mattarollo, S. R., Rahimpour, A., Choyce, A., Godfrey, D. I., Leggatt, G. R., Frazer, I. H. (2010) Invariant NKT cells in hyperplastic skin induce a local immune suppressive environment by IFN-γ production. J. Immunol. 184, 1242-1250.
12. Ilan, Y. (2009) α Versus β: are we on the way to resolve the mystery as to which is the endogenous ligand for natural killer T cells? Clin. Exp. Immunol. 158, 300-307.
13. Zhou, D., Mattner, J., Cantu, C., 3rd, Schrantz, N., Yin, N., Gao, Y., Sagiv, Y., Hudspeth, K., Wu, Y. P., Yamashita, T., Teneberg, S., Wang, D., Proia, R. L., Levery, S. B., Savage, P. B., Teyton, L., Bendelac, A. (2004) Lysosomal glycosphingolipid recognition by NKT cells. Science 306, 1786-1789.
14. Mattner, J., Debord, K. L., Ismail, N., Goff, R. D., Cantu, C., 3rd, 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. (2005) Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections. Nature 434, 525-529.
15. Giabbai, B., Sidobre, S., Crispin, M. D., Sanchez-Ruiz, Y., Bachi, A., Kronenberg, M., Wilson, I. A., Degano, M. (2005) Crystal structure of mouse CD1d bound to the self ligand phosphatidylcholine: a molecular basis for NKT cell activation. J. Immunol. 175, 977-984.
16. De Silva, A. D., Park, J. J., Matsuki, N., Stanic, A. K., Brutkiewicz, R. R., Medof, M. E., Joyce, S. (2002) Lipid protein interactions: the assembly of CD1d1 with cellular phospholipids occurs in the endoplasmic reticulum. J. Immunol. 168, 723-733.
17. Lalazar, G., Preston, S., Zigmond, E., Ben Yaacov, A., Ilan, Y. (2006) Glycolipids as immune modulatory tools. Mini Rev. Med. Chem. 6, 1249-1253.
18. Chan, A. C., Leeansyah, E., Cochrane, A., d'Udekem d'Acoz, Y., Mittag, D., Harrison, L. C., Godfrey, D. I., Berzins, S. P. (2013) Ex-vivo analysis of human natural killer T cells demonstrates heterogeneity between tissues and within established CD4(+) and CD4(+) subsets. Clin. Exp. Immunol. 172, 129-137.
19. Crowe, N. Y., Coquet, J. M., Berzins, S. P., Kyparissoudis, K., Keating, R., Pellicci, D. G., Hayakawa, Y., Godfrey, D. I., Smyth, M. J. (2005) Differential antitumor immunity mediated by NKT cell subsets in vivo. J. Exp. Med. 202, 1279-1288.
20. McKee, S. J., Young, V. L., Clow, F., Hayman, C. M., Baird, M. A., Hermans, I. F., Young, S. L., Ward, V. K. (2012) Virus-like particles and γ-galactosylceramide form a self-adjuvanting composite particle that elicits anti-tumor responses. J. Control Release 159, 338-345.
21. Petersen, T. R., Sika-Paotonu, D., Knight, D. A., Dickgreber, N., Farrand, K. J., Ronchese, F., Hermans, I. F. (2010) Potent anti-tumor responses to immunization with dendritic cells loaded with tumor tissue and an NKT cell ligand. Immunol. Cell. Biol. 88, 596-604.
22. Mattarollo, S. R., Smyth, M. J. (2013) NKT cell adjuvants in therapeutic vaccines against hematological cancers. Oncoimmunology 2, e22615.
23. Mattarollo, S. R., West, A. C., Steegh, K., Duret, H., Paget, C., Martin, B., Matthews, G. M., Shortt, J., Chesi, M., Bergsagel, P. L., Bots, M., Zuber, J., Lowe, S. W., Johnstone, R. W., Smyth, M. J. (2012) NKT cell adjuvant-based tumor vaccine for treatment of myc oncogene-driven mouse B-cell lymphoma. Blood 120, 3019-3029.
24. Fujita, H., Teng, A., Nozawa, R., Takamoto-Matsui, Y., Katagiri-Matsumura, H., Ikezawa, Z., Ishii, Y. (2009) Production of both IL-27 and IFN-γ after the treatment with a ligand for invariant NK T cells is responsible for the suppression of Th2 response and allergic inflammation in a mouse experimental asthma model. J. Immunol. 183, 254-260.
25. Patel, O., Pellicci, D. G., Gras, S., Sandoval-Romero, M. L., Uldrich, A. P., Mallevaey, T., Clarke, A. J., Le Nours, J., Theodossis, A., Cardell, S. L., Gapin, L., Godfrey, D. I., Rossjohn, J. (2012) Recognition of CD1d-sulfatide mediated by a type II natural killer T cell antigen receptor. Nat. Immunol. 13, 857-863.
26. Blomqvist, M., Rhost, S., Teneberg, S., Lofbom, L., Osterbye, T., Brigl, M., Mansson, J. E., Cardell, S. L. (2009) Multiple tissue-specific isoforms of sulfatide activate CD1d-restricted type II NKT cells. Eur. J. Immunol. 39, 1726-1735.
27. Terabe, M., Swann, J., Ambrosino, E., Sinha, P., Takaku, S., Hayakawa, Y., Godfrey, D. I., Ostrand-Rosenberg, S., Smyth, M. J., Berzofsky, J. A. (2005) A nonclassical non-Vα14Jα18 CD1d-restricted (type II) NKT cell is sufficient for down-regulation of tumor immunosurveillance. J. Exp. Med. 202, 1627-1633.
28. Terabe, M., Berzofsky, J. A. (2007) NKT cells in immunoregulation of tumor immunity: a new immunoregulatory axis. Trends Immunol. 28, 491-496.
29. Berzofsky, J. A., Terabe, M. (2009) The contrasting roles of NKT cells in tumor immunity. Curr. Mol. Med. 9, 667-672.
30. Patel, O., Pellicci, D. G., Uldrich, A. P., Sullivan, L. C., Bhati, M., McKnight, M., Richardson, S. K., Howell, A. R., Mallevaey, T., Zhang, J., Bedel, R., Besra, G. S., Brooks, A. G., Kjer-Nielsen, L., McCluskey, J., Porcelli, S. A., Gapin, L., Rossjohn, J., Godfrey, D. I. (2011) Vβ2 natural killer T cell antigen receptor-mediated recognition of CD1d-glycolipid antigen. Proc. Natl. Acad. Sci. USA 108, 19007-19012.
31. Linsen, L., Thewissen, M., Baeten, K., Somers, V., Geusens, P., Raus, J., Stinissen, P. (2005) Peripheral blood but not synovial fluid natural killer T cells are biased towards a Th1-like phenotype in rheumatoid arthritis. Arthritis Res. Ther. 7, R493-R502.
32. Zhao, Y., Fishelevich, R., Petrali, J. P., Zheng, L., Anatolievna, M. A., Deng, A., Eckert, R. L., Gaspari, A. A. (2008) Activation of keratinocyte protein kinase C ζ in psoriasis plaques. J. Invest. Dermatol. 128, 2190-2197.
33. Kono, F., Honda, T., Aini, W., Manabe, T., Haga, H., Tsuruyama, T. (2013) IFN-γ/CCR5 expression in invariant NKT cells and CCL5 expression in capillary veins of dermal papillae correlate with development of psoriasis vulgaris. Br. J. Dermatol. doi: 10.1111/bjd.12812 [Epub ahead of print].
34. Peternel, S., Kastelan, M. (2009) Immunopathogenesis of psoriasis: focus on natural killer T cells. J. Eur. Acad. Dermatol. Venereol. 23, 1123-1127.
35. Balato, A., Unutmaz, D., Gaspari, A. A. (2009) Natural killer T cells: an unconventional T-cell subset with diverse effector and regulatory functions. J. Invest. Dermatol. 129, 1628-1642.
36. Nickoloff, B. J., Bonish, B., Huang, B. B., Porcelli, S. A. (2000) Characterization of a T cell line bearing natural killer receptors and capable of creating psoriasis in a SCID mouse model system. J. Dermatol. Sci. 24, 212-225.
37. Moodycliffe, A. M., Nghiem, D., Clydesdale, G., Ullrich, S. E. (2000) Immune suppression and skin cancer development: regulation by NKT cells. Nat. Immunol. 1, 521-525.
38. Fukunaga, A., Khaskhely, N. M., Ma, Y., Sreevidya, C. S., Taguchi, K., Nishigori, C., Ullrich, S. E. (2010) Langerhans cells serve as immunoregulatory cells by activating NKT cells. J. Immunol. 185, 4633-4640.
39. Mittal, D., Kassianos, A. J., Tran, L. S., Bergot, A. S., Gosmann, C., Hofmann, J., Blumenthal, A., Leggatt, G. R., Frazer, I. H. (2013) Indoleamine 2,3-dioxygenase activity contributes to local immune suppression in the skin expressing human papillomavirus oncoprotein E7. J. Invest. Dermatol. 133, 2686-2694.
40. Oh, K., Kim, S., Park, S. H., Gu, H., Roopenian, D., Chung, D. H., Kim, Y. S., Lee, D. S. (2005) Direct regulatory role of NKT cells in allogeneic graft survival is dependent on the quantitative strength of antigenicity. J. Immunol. 174, 2030-2036.
41. Goubier, A., Vocanson, M., Macari, C., Poyet, G., Herbelin, A., Nicolas, J. F., Dubois, B., Kaiserlian, D. (2013) Invariant NKT cells suppress CD8(+) T-cell-mediated allergic contact dermatitis independently of regulatory CD4(+) T cells. J. Invest. Dermatol. 133, 980-987.
42. Cancer Australia and Authoritative Information and Statisticsto Promote Better Health and Wellbeing (2008) Non-melanoma skin cancer: general practice consultations, hospitalisation and mortality. Cancer Series 43, Cat. No. CAN 39. Canberra: AIHW. AIHW, C. A. (2008) Non-melanoma skin cancer: general practice consultations, hospitalisation and mortality. In Cancer Series 43, Cat. no. CAN 39. AIHW, Canberra, Australia.
43. Preston, D. S., Stern, R. S. (1992) Nonmelanoma cancers of the skin. N. Engl. J. Med. 327, 1649-1662.
44. Armstrong, B. K., Kricker, A. (2001) The epidemiology of UV induced skin cancer. J. Photochem. Photobiol. B 63, 8-18.
45. Brash, D. E., Rudolph, J. A., Simon, J. A., Lin, A., McKenna, G. J., Baden, H. P., Halperin, A. J., Ponten, J. (1991) A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Proc. Natl. Acad. Sci. USA 88, 10124-10128.
46. Ananthaswamy, H. N., Loughlin, S. M., Cox, P., Evans, R. L., Ullrich, S. E., Kripke, M. L. (1997) Sunlight and skin cancer: inhibition of p53 mutations in UV-irradiated mouse skin by sunscreens. Nat. Med. 3, 510-514.
47. Pierceall, W. E., Kripke, M. L., Ananthaswamy, H. N. (1992) N-ras mutation in ultraviolet radiation-induced murine skin cancers. Cancer Res. 52, 3946-3951.
48. Bowden, G. T. (2004) Prevention of non-melanoma skin cancer by targeting ultraviolet-B-light signalling. Nat. Rev. Cancer 4, 23-35.
49. Fisher, M. S., Kripke, M. L. (1982) Suppressor T lymphocytes control the development of primary skin cancers in ultraviolet-irradiated mice. Science 216, 1133-1134.
50. Ullrich, S. E. (2005) Mechanisms underlying UV-induced immune suppression. Mutat. Res. 571, 185-205.
51. Ullrich, S. E., Byrne, S. N. (2012) The immunologic revolution: photoimmunology. J. Invest. Dermatol. 132, 896-905.
52. Kripke, M. L. (1974) Antigenicity of murine skin tumors induced by ultraviolet light. J. Natl. Cancer Inst. 53, 1333-1336.
53. Byrne, S. N., Ahmed, J., Halliday, G. M. (2005) Ultraviolet B but not A radiation activates suppressor B cells in draining lymph nodes. Photochem. Photobiol. 81, 1366-1370.
54. Byrne, S. N., Halliday, G. M. (2005) B Cells activated in lymph nodes in response to ultraviolet irradiation or by interleukin-10 inhibit dendritic cell induction of immunity. J. Invest. Dermatol. 124, 570-578.
55. Loser, K., Mehling, A., Loeser, S., Apelt, J., Kuhn, A., Grabbe, S., Schwarz, T., Penninger, J. M., Beissert, S. (2006) Epidermal RANKL controls regulatory T-cell numbers via activation of dendritic cells. Nat. Med. 12, 1372-1379.
56. Pellicci, D. G., Hammond, K. J., Coquet, J., Kyparissoudis, K., Brooks, A. G., Kedzierska, K., Keating, R., Turner, S., Berzins, S., Smyth, M. J., Godfrey, D. I. (2005) DX5/CD49b-positive T cells are not synonymous with CD1d-dependent NKT cells. J. Immunol. 175, 4416-4425.
57. Matsumura, Y., Moodycliffe, A. M., Nghiem, D. X., Ullrich, S. E., Ananthaswamy, H. N. (2004) Resistance of CD1d-/-mice to ultravioletinduced skin cancer is associated with increased apoptosis. Am. J. Pathol. 165, 879-887.
58. Ryser, S., Schuppli, M., Gauthier, B., Rivero Hernandez, D., Roye, O., Hohl, D., German, B., Holzwarth, J. A., Moodycliffe, A. M. (2014) UVBinduced skin inflammation and cutaneous tissue injury is dependent on the MHC class I-like protein, CD1d. J. Invest. Dermatol. 134, 192-202.
59. Takagi, Y., Nakagawa, H., Yaginuma, T., Takema, Y., Imokawa, G. (2005) An accumulation of glucosylceramide in the stratum corneum due to attenuated activity of β-glucocerebrosidase is associated with the early phase of UVB-induced alteration in cutaneous barrier function. Arch. Dermatol. Res. 297, 18-25.
60. Ilan, Y., Ohana, M., Pappo, O., Margalit, M., Lalazar, G., Engelhardt, D., Rabbani, E., Nagler, A. (2007) Alleviation of acute and chronic graft-versushost disease in a murine model is associated with glucocerebroside-enhanced natural killer T lymphocyte plasticity. Transplantation 83, 458-467.
61. Brennan, P. J., Tatituri, R. V., Brigl, M., Kim, E. Y., Tuli, A., Sanderson, J. P., Gadola, S. D., Hsu, F. F., Besra, G. S., Brenner, M. B. (2011) Invariant natural killer T cells recognize lipid self antigen induced by microbial danger signals. Nat. Immunol. 12, 1202-1211.
62. Stanic, A. K., De Silva, A. D., Park, J. J., Sriram, V., Ichikawa, S., Hirabyashi, Y., Hayakawa, K., Van Kaer, L., Brutkiewicz, R. R., Joyce, S. (2003) Defective presentation of the CD1d1-restricted natural Va14Ja18 NKT lymphocyte antigen caused by β-D-glucosylceramide synthase deficiency. Proc. Natl. Acad. Sci. USA 100, 1849-1854.
63. Faergemann, J., Larko, O. (1987) The effect of UV-light on human skin microorganisms. Acta Derm. Venereol. 67, 69-72.
64. Wei, B., Wingender, G., Fujiwara, D., Chen, D. Y., McPherson, M., Brewer, S., Borneman, J., Kronenberg, M., Braun, J. (2010) Commensal microbiota and CD8+ T cells shape the formation of invariant NKT cells. J. Immunol. 184, 1218-1226.
65. Webb, A. R., DeCosta, B. R., Holick, M. F. (1989) Sunlight regulates the cutaneous production of vitamin D3 by causing its photodegradation. J. Clin. Endocrinol. Metab. 68, 882-887.
66. Mora, J. R., Iwata, M., von Andrian, U. H. (2008) Vitamin effects on the immune system: vitamins A and D take centre stage. Nat. Rev. Immunol. 8, 685-698.
67. Yu, S., Cantorna, M. T. (2008) The vitamin D receptor is required for iNKT cell development. Proc. Natl. Acad. Sci. USA 105, 5207-5212.
68. Ooi, J. H., Chen, J., Cantorna, M. T. (2012) Vitamin D regulation of immune function in the gut: why do T cells have vitamin D receptors? Mol. Aspects Med. 33, 77-82.
69. Dam, T. N., Moller, B., Hindkjaer, J., Kragballe, K. (1996) The vitamin D3 analog calcipotriol suppresses the number and antigen-presenting function of Langerhans cells in normal human skin. J. Investig. Dermatol. Symp. Proc. 1, 72-77.
70. Meindl, S., Rot, A., Hoetzenecker, W., Kato, S., Cross, H. S., Elbe-Burger, A. (2005) Vitamin D receptor ablation alters skin architecture and homeostasis of dendritic epidermal T cells. Br. J. Dermatol. 152, 231-241.
71. Ghoreishi, M., Bach, P., Obst, J., Komba, M., Fleet, J. C., Dutz, J. P. (2009) Expansion of antigen-specific regulatory T cells with the topical vitamin D analog calcipotriol. J. Immunol. 182, 6071-6078.
72. Wang, L., Jameson, S. C., Hogquist, K. A. (2009) Epidermal Langerhans cells are not required for UV-induced immunosuppression. J. Immunol. 183, 5548-5553.
73. Mattarollo, S. R., Yong, M., Gosmann, C., Choyce, A., Chan, D., Leggatt, G. R., Frazer, I. H. (2011) NKT cells inhibit antigen-specific effector CD8 T cell induction to skin viral proteins. J. Immunol. 187, 1601-1608.
74. Mattarollo, S. R., Yong, M., Tan, L., Frazer, I. H., Leggatt, G. R. (2010) Secretion of IFN-γ but not IL-17 by CD1d-restricted NKT cells enhances rejection of skin grafts expressing epithelial cell-derived antigen. J. Immunol. 184, 5663-5669.
75. Iwai, T., Tomita, Y., Okano, S., Shimizu, I., Yasunami, Y., Kajiwara, T., Yoshikai, Y., Taniguchi, M., Nomoto, K., Yasui, H. (2006) Regulatory roles of NKT cells in the induction and maintenance of cyclophosphamide-induced tolerance. J. Immunol. 177, 8400-8409.
76. Iwai, T., Tomita, Y., Shimizu, I., Kajiwara, T., Onzuka, T., Okano, S., Yasunami, Y., Yoshikai, Y., Nomoto, K., Tominaga, R. (2007) The immunoregulatory roles of natural killer T cells in cyclophosphamide-induced tolerance. Transplantation 84, 1686-1695.
77. Onzuka, T., Tomita, Y., Shimizu, I., Okano, S., Yamada, H., Yoshikai, Y., Tominaga, R. (2008) Role of the cytokine profiles produced by invariant natural killer T cells in the initial phase of cyclophosphamide-induced tolerance. Transplantation 86, 1301-1310.
78. Zeng, D., Lewis, D., Dejbakhsh-Jones, S., Lan, F., Garcia-Ojeda, M., Sibley, R., Strober, S. (1999) Bone marrow NK1.1(-) and NK1.1(+) T cells reciprocally regulate acute graft versus host disease. J. Exp. Med. 189, 1073-1081.
79. Leveson-Gower, D. B., Olson, J. A., Sega, E. I., Luong, R. H., Baker, J., Zeiser, R., Negrin, R. S. (2011) Low doses of natural killer T cells provide protection from acute graft-versus-host disease via an IL-4-dependent mechanism. Blood 117, 3220-3229.
80. Matsumoto, K., Leggatt, G. R., Zhong, J., Liu, X., de Kluyver, R. L., Peters, T., Fernando, G. J., Liem, A., Lambert, P. F., Frazer, I. H. (2004) Impaired antigen presentation and effectiveness of combined active/passive immunotherapy for epithelial tumors. J. Natl. Cancer Inst. 96, 1611-1619.
81. Askenase, P. W., Majewska-Szczepanik, M., Kerfoot, S., Szczepanik, M. (2011) Participation of iNKT cells in the early and late components of Tc1-mediated DNFB contact sensitivity: cooperative role of αβ-T cells. Scand. J. Immunol. 73, 465-477.
82. Nieuwenhuis, E. E., Gillessen, S., Scheper, R. J., Exley, M. A., Taniguchi, M., Balk, S. P., Strominger, J. L., Dranoff, G., Blumberg, R. S., Wilson, S. B. (2005) CD1d and CD1d-restricted iNKT-cells play a pivotal role in contact hypersensitivity. Exp. Dermatol. 14, 250-258.
83. Eguchi, T., Kumagai, K., Kobayashi, H., Shigematsu, H., Kitaura, K., Suzuki, S., Horikawa, T., Hamada, Y., Ogasawara, K., Suzuki, R. (2013) Accumulation of invariant NKT cells into inflamed skin in a novel murine model of nickel allergy. Cell. Immunol. 284, 163-171.
84. Simon, D., Kozlowski, E., Simon, H. (2009) Natural killer T cells expressing IFN-γ and IL-4 in lesional skin of atopic eczema. Allergy 64, 1681-1684.
85. Takahashi, T., Nakamura, K., Chiba, S., Kanda, Y., Tamaki, K., Hirai, H. (2003) V α 24+ Natural killer T cells are markedly decreased in atopic dermatitis patients. Hum. Immunol. 64, 586-592.
86. Campos, R. A., Szczepanik, M., Itakura, A., Akahira-Azuma, M., Sidobre, S., Kronenberg, M., Askenase, P. W. (2003) Cutaneous immunization rapidly activates liver invariant Vα14 NKT cells stimulating B-1 B cells to initiate T cell recruitment for elicitation of contact sensitivity. J. Exp. Med. 198, 1785-1796.