ROLE OF MACROPHAGES AND ALPHA-BETA-T-LYMPHOCYTES IN EARLY INTERLEUKIN-10 PRODUCTION DURING LISTERIA-MONOCYTOGENES INFECTION

Immunity to intracellular bacteria including Listeria monocytogenes is determined by T(h)1 cells and CD8 T cells which produce interferon-ga mma. Here we show that high levels of IL-10 are released by splenocyte s from mice infected with L. monocytogenes. IL-10 was detected on day 1 after infection, peaked on day 4, and subsequently declined. Cell se paration studies and experiments with RAG-1-deficient mice, which do n ot possess mature B cells or T cells, revealed that the macrophage is the major cellular source of early IL-10 production. Elevated IL-10 pr oduction in RAG-1 mutants and TCRbeta mutants, but not in TCRdelta mut ants, is consistent with an inhibition of macrophage IL-10 release by alphabeta T cells. High IL-10 production was also seen after infection with another intracellular bacterium, Mycobacterium bovis. Since IL-1 0 inhibits T(h)1 cell responses, certain pathogens might use induction of this cytokine as an evasion mechanism from the protective immune r esponse of the host. However, our findings showing high levels of IL-1 0 production in infectious models which are dominated by T(h)1 cell re sponses suggest that IL-10 alone is insufficient for directing T(h)0 d ifferentiation into the T(h)2 cell pathway. These findings therefore c hallenge the view of IL-10 as a unique and decisive determinator of th e T(h)2 cell pathway.