MHC class II-KO mice are resistant to the immunosuppressive effects of UV light

Eur J Dermatol. Jan-Feb 2002;12(1):10-9.

Abstract

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.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / radiation effects*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / radiation effects*
  • Dendritic Cells / immunology
  • Dendritic Cells / radiation effects
  • Dermatitis, Contact / immunology*
  • Dinitrofluorobenzene
  • Disease Models, Animal
  • Dose-Response Relationship, Radiation
  • Haptens / immunology
  • Immunosuppression
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nitrobenzenes
  • Skin / immunology
  • Skin / radiation effects
  • Ultraviolet Rays / adverse effects

Substances

  • Haptens
  • Nitrobenzenes
  • Dinitrofluorobenzene