Interferon-gamma inhibits tumor antigen presentation by epidermal antigen-presenting cells.
Murine I-A+ epidermal antigen-presenting cells (APCs) have been shown to be capable of presenting soluble tumor fragments (TFs), as a source of tumor-associated antigens (TAAs), for primary and secondary tumor immune responses. In this study we investigated whether incubation of epidermal APCs in interferon-gamma (IFN-gamma) modulates their ability to present TAA and whether the effects of IFN-gamma on the presentation of tumor antigen correspond to its effects on alloantigen presentation in both primed and unprimed systems. Our results show that three weekly subcutaneous injections of naive mice with GM-CSF-cultured but not with fresh TAA-pulsed epidermal APCs induce protective tumor immunity in naive mice and that the immunostimulatory effect of GM-CSF in this system is abrogated by coculture of epidermal cells in IFN-gamma. Furthermore, epidermal APCs are able to present TAA to primed, tumor-immune mice, as assessed by the elicitation of tumor-specific delayed-type hypersensitivity after injection of TAA-pulsed epidermal APCs. IFN-gamma was found to inhibit tumor antigen presentation by freshly prepared epidermal APCs in this system. The effects of IFN-gamma on the presentation of tumor antigen correlated well with its effects on the primary and secondary mixed epidermal cell-lymphocyte reaction, indicating that IFN-gamma differentially modulates the function of epidermal APCs with regard to induction versus elicitation of immunity.
Grabbe
S
S
Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Charlestown 02129.
Bruvers
S
S
Beissert
S
S
Granstein
R D
RD
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000187:drug effects; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007106:Immune Sera / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D007801:Langerhans Cells / Q000276:immunology*; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D011994:Recombinant Proteins; D012513:Sarcoma, Experimental / Q000276:immunology*; D012867:Skin / Q000276:immunology*
D000951:Antigens, Neoplasm; D007106:Immune Sera; D011994:Recombinant Proteins; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor