IL-10 inhibits alloreactive cytotoxic T lymphocyte generation in vivo.
In this report, we present evidence that the CTL response directed against MHC Class I allo-determinants can be inhibited as a result of IL-10 expression in vivo. The presence of localized IL-10 secretion at the site of allogeneic tumor cell challenge resulted in marked inhibition of the CTL response and allowed growth of the tumor in the allogeneic host. Using purified CD4+ T cells from mice immunized in the presence or absence of IL-10, we have shown that the loss of alloreactivity as a consequence of IL-10 expression results from the inhibition of CD4+ T cell function. The expression of either IL-2 or IFN-gamma with IL-10 locally at the time of allogeneic cell challenge completely restored CTL alloreactivity, suggesting that the action of IL-10 could be bypassed by providing helper T lymphocyte-derived cytokines of the Th1 type at the site of immunization. Inhibition of alloreactivity by IL-10 was observed using either purified macrophages or dendritic cells as APC in an in vitro assay. Thus, the expression of IL-10 following antigenic challenge (such as that observed in Th2-like immune responses) may profoundly limit the ability for generating functional CTL in vivo.
Wang
L
L
MGH Cancer Center, Massachusetts General Hospital, Charlestown 02129.
Goillot
E
E
Tepper
R I
RI
D000818:Animals; D000911:Antibodies, Monoclonal; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003001:Cloning, Molecular; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D005455:Fluorescent Antibody Technique; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology
D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D007519:Isoantigens; D016753:Interleukin-10; D007371:Interferon-gamma