SECONDARY RESPONSE TO LISTERIA INFECTION REQUIRES IFN-GAMMA BUT IS PARTIALLY INDEPENDENT OF IL-12

During a secondary immune response to Listeria monocytogenes (LM), the production of IFN-gamma was still required for resistance, but it was considerably less dependent on IL-12 production. When IL-12 was neutr alized in vivo using specific hamster antimurine IL-12 mAbs, there was a dramatically increased susceptibility to infection during primary l isteriosis but much less during a secondary infection. However, neutra lization of IFN-gamma in vivo resulted in a similar increased suscepti bility during both primary and secondary listeriosis. In culture, sple nocytes isolated from unimmunized mice produced IFN-gamma in response to heat-killed L. monocytogenes (hk-LM) that was absolutely dependent upon IL-12 production. However, directly stimulating the TCR with anti -CD3-epsilon mAbs resulted in IFN-gamma production that was unaffected by neutralizing IL-12 in vitro. In contrast, splenocytes isolated fro m LM-immune mice produced IFN-gamma in response to hk-LM, part of whic h was independent on IL-12 production. However, anti-CD3-epsilon Ab-st imulated IFN-gamma production remained independent of IL-12 production . The source of hk-LM-induced, IL-12-independent IFN-gamma production was the T cell because anti-Thy1.2 Ab plus complement treatment in vit ro completely abolished it. Together, these data support a model of me mory T cells being produced during the primary infection with LM that can be stimulated to produce IFN-gamma during the secondary response t o LM, partially independent of macrophage IL-12 production.