Dendritic epidermal T cells in ultraviolet-irradiated skin enhance skin tumor growth by inhibiting CD4+ T-cell-mediated immunity.
Chronic UV irradiation of the skin not only causes skin cancer in humans but modifies immune responses generated within the epidermis, resulting in impaired immunity against a variety of infectious as well as noninfectious agents. In mice, tumors induced by chronic UV irradiation grow faster when transplanted into mice that are immunosuppressed by UV irradiation. To investigate epidermal cells (EC) in UV-irradiated skin that inhibit the induction of immunity against tumors, the murine UV-induced LK2 regresser tumor was used. This tumor grows initially in vivo and then spontaneously regresses. In vivo T-cell depletion was used to determine that regression of LK2 tumors in unirradiated mice was mediated mainly by CD8+ T lymphocytes, with minor involvement of CD4+ T cells. Immunization of mice with tumor antigen-pulsed EC prepared from unirradiated mice enhanced immunity against subsequent inoculation of LK2 tumors, augmenting regression of the LK2 tumor due to increased activation of both CD4+ and CD8+ T-cell subsets against the tumor. By contrast, immunization with EC prepared from UV-irradiated skin inhibited the induction of antitumor immunity, enhancing LK2 tumor growth. This was caused by the dendritic epidermal T cells that remained within this UV-irradiated EC preparation inhibiting activation of CD4+ T cells, without affecting CD8+ T cell function. Hence, during the development of murine UV-induced skin tumors, dendritic epidermal T cell inhibition of CD4+ T cell activation may enable this skin tumor to escape immune-mediated destruction.
Cavanagh
L L
LL
Department of Medicine (Dermatology), University of Sydney at Royal Prince Alfred Hosptital, Camperdown, NSW, Australia.
Halliday
G M
GM
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004817:Epidermis / Q000276:immunology; D005260:Female; D006084:Graft Rejection; D007108:Immune Tolerance; D007111:Immunity, Cellular / Q000528:radiation effects; D008213:Lymphocyte Activation / Q000528:radiation effects; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009381:Neoplasms, Radiation-Induced / Q000209:etiology* / Q000276:immunology; D012867:Skin / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000209:etiology* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013997:Time Factors; D014466:Ultraviolet Rays