DIFFERENTIAL-EFFECTS OF VIABLE AND KILLED BACTERIA ON IL-12 EXPRESSION OF MACROPHAGES

Listeria monocytogenes-specific, IFN-gamma-producing CD4(+) T cells ar e induced in 5-day in vitro cultures of naive spleen cells with viable L. monocytogenes (VLM) but are not induced in cultures with heat kill ed L. monocytogenes (HKLM). Anti-IL-12 Abs abrogated the induction of the IFN-gamma-producing CD4(+) T cells by VLM, suggesting an importanc e of IL-12 in the induction of IFN-gamma-producing CD4(+) T cells, Acc ordingly, IL-12p40 was expressed by macrophages (M phi) from the cultu res of whole spleen cells with VLM but not with HKLM, although HKLM in duced IL-12p40 expression on M phi when nonadherent cells were removed before culture, In vivo analysis also showed that VLM induced IL-12p4 0 expression by M phi, whereas HKLM failed to induce it. On the other hand, the addition of anti-IL-10 mAb into cultures of whole spleen cel ls and HKLM resulted in an increase of IL-12p40 expression by M phi. F urthermore, we detected an expression of IFN-gamma by both adherent an d nonadherent spleen cells at the early stage of stimulation with VLM before the appearance of IFN-gamma-producing CD4(+) T cells, These dat a suggest that HKLM induce nonadherent spleen cells to produce IL-10 w hich may down-regulate IFN-gamma-producing CD4(+) T cells by blocking IL-12 production by M phi. In contrast, VLM support IFN-gamma producti on by CD4(+) T cells by stimulating M phi to produce IL-12 and IFN-gam ma.