MHC class II-KO mice are resistant to the immunosuppressive effects of UV light.
Ultraviolet B light is responsible for the development of skin cancer through inhibition of cellular immune responses in the skin. Here, we addressed the question of the mechanisms involved in UVB-induced immune suppression. We used a model of antigen-specific skin inflammation, the contact hypersensitivity (CHS) reaction to DNFB, which is mediated by CD8+ effector T cells and down-regulated by CD4+ T cells. We show that UVB have opposite effects on CD4+ and CD8+ T cells. UVB irradiation reduced the number of activated CD8+ T cells in the lymphoid organs and impaired their functional activity. This resulted in deficient infiltration of IFN-gamma producing CD8+ T cells at challenged site and consequently in the inability to develop an antigen-specific CHS reaction. This effect is mediated by CD4+ suppressor cells, since in the absence of CD4+ T cells (MHC class II-KO mice and CD4+ T cell-depleted mice), UVB have no immunosuppressive effects. Indeed, UVB-irradiated CD4+ T cell-deficient mice have a normal frequency of IFN-gamma-producing hapten-specific CD8+ T cells in the lymphoid organs and develop a normal CHS reaction to DNFB. Thus, in the absence of CD4+ T cells, UVB do not alter the priming of MHC class I-restricted CD8+ effector T cells. Collectively, these data show that UVB-induced immune suppression is secondary to preferential activation of CD4+ suppressor T cells and not to deficient priming and expansion of the effector CD8+ T cell population. This may have important implications for the prevention of UV-induced skin cancers.
Krasteva
Maya
M
Institut National de la Santé et de la Recherche Médicale (INSERM) U. 503, 21, avenue Tony-Garnier, 69365 Lyon Cedex 07, France.
Aubin
François
F
Laventurier
Sandrine
S
Kehren
Jeanne
J
Assossou
Olga
O
Kanitakis
Jean
J
Kaiserlian
Dominique
D
Nicolas
Jean-François
JF
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000528:radiation effects*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000528:radiation effects*; D003713:Dendritic Cells / Q000276:immunology / Q000528:radiation effects; D003877:Dermatitis, Contact / Q000276:immunology*; D004139:Dinitrofluorobenzene; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D006241:Haptens / Q000276:immunology; D007165:Immunosuppression Therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009578:Nitrobenzenes; D012867:Skin / Q000276:immunology / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects
D006241:Haptens; D009578:Nitrobenzenes; D004139:Dinitrofluorobenzene