Secondary response to Listeria infection requires IFN-γ but is partially independent of IL-12

During a secondary immune response to Listeria monocytogenes (LM), the production of IFN-γ was still required for resistance, but it was considerably less dependent on IL-12 production. When IL-12 was neutralized in vivo using specific hamster antimurine IL-12 mAbs, there was a dramatically increased susceptibility to infection during primary listeriosis but much less during a secondary infection. However, neutralization of IFN- γ in vivo resulted in a similar increased susceptibility during both primary and secondary listeriosis. In culture, splenocytes isolated from unimmunized mice produced IFN-γ 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-ε mAbs resulted in IFN-γ production that was unaffected by neutralizing IL-12 in vitro. In contrast, splenocytes isolated from LM-immune mice produced IFN-γ in response to hk-LM, part of which was independent on IL-12 production. However, anti-CD3-ε Ab-stimulated IFN-γ production remained independent of IL-12 production. The source of hk-LM- induced, IL-12-independent IFN-γ production was the T cell because anti- Thy1.2 Ab plus complement treatment in vitro completely abolished it. Together, these data support a model of memory T cells being produced during the primary infection with LM that can be stimulated to produce IFN-γ during the secondary response to LM, partially independent of macrophage IL-12 production.