Dendritic epidermal T-cell involvement in induction of CD8+ T cell-mediated immunity against an ultraviolet radiation-induced skin tumor.
Murine epidermis contains 2 distinct cell populations which contribute to the skin immune system, Langerhans cells (LC), and dendritic epidermal T cells (DETC). LCs are important in the induction of immunity against a wide range of antigens; however, the function of DETC is unclear. To investigate the roles of these epidermal cells (EC) in protective antitumor immunity, an in vivo model of an ultraviolet radiation-induced fibrosarcoma, UV-13-1, was used. Mice were immunized with tumor antigen-pulsed EC followed 10 days later by an injection into the ear of 10(5) tumor cells, which did not lead to formation of a detectable tumor, but was intended to simulate the influence of a developing tumor on the ensuing immune response. The mice were then challenged with 2 x 10(6) viable tumor cells in each flank, sufficient to result in growth of a measurable tumor. Protective immunity was induced by DETC, and shown to be long-lasting, with tumors inoculated 160 days after immunization being effectively rejected. The effector cells responsible for protective immunity were CD8+ T cells. Delayed-type hypersensitivity generated by tumor antigen-pulsed EC was dependent on LCs, with no involvement of DETCs. This response, in contrast to that of DETC, required prior culture of EC with GM-CSF, but failed to inhibit tumor growth or incidence. Thus DETC and LC can both activate antitumor immune responses, although only the DETC-dependent response results in protective immunity in the presence of a developing tumor.
Cavanagh
L L
LL
Department of Medicine (Dermatology), University of Sydney at Royal Prince Alfred Hospital, Camperdown, Australia. loisc@gpo.pa.uq.edu.au
Barnetson
R S
RS
Basten
A
A
Halliday
G M
GM
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007111:Immunity, Cellular / Q000276:immunology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009381:Neoplasms, Radiation-Induced / Q000276:immunology*; D012878:Skin Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D016178:Granulocyte-Macrophage Colony-Stimulating Factor