IL-10 INHIBITS ALLOREACTIVE CYTOTOXIC T-LYMPHOCYTE GENERATION IN-VIVO

In this report, we present evidence that the CTL response directed aga inst MHC Class I allodeterminants can be inhibited as a result of IL-1 0 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 presen ce 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 CD 4(+) T cell function. The expression of either IL-2 or IFN-gamma with IL-10 locally at the time of allogeneic cell challenge completely rest ored 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 a s APC in an in vitro assay. Thus, the expression of IL-10 following an tigenic challenge (such as that observed in Th2-like immune responses) may profoundly limit the ability for generating functional CTL in viv o. (C) 1994 Academic Press, Inc.