Adaptive Immunity and Enhanced CD8+ T Cell Response to Listeria monocytogenes in the Absence of Perforin and IFN-γ

Abstract

Single Ag-specific CD8+ T cells from IFN-γ-deficient (GKO) or perforin-deficient (PKO) mice provide substantial immunity against murine infection with Listeria monocytogenes. To address the potential for redundancy between perforin and IFN-γ as CD8+ T cell effector mechanisms, we generated perforin/IFN-γ (PKO/GKO) double-deficient mice. PKO/GKO-derived CD8+ T cells specific for the immunodominant listeriolysin O (LLO91–99) epitope provide immunity to LM infection similar to that provided by Ag-matched wild-type (WT) CD8+ T cells in the liver but reduced in the spleen. Strikingly, polyclonal CD8+ T cells from immunized PKO/GKO mice were ∼100-fold more potent in reducing bacterial numbers than the same number of polyclonal CD8+ T cells from immunized WT mice. This result is probably quantitative, because the frequency of the CD8+ T cell response against the immunodominant LLO91–99 epitope is >4.5-fold higher in PKO/GKO mice than WT mice at 7 days after identical immunizations. Moreover, PKO/GKO mice can be immunized by a single infection with attenuated Listeria to resist >80,000-fold higher challenges with virulent organisms than naive PKO/GKO mice. These data demonstrate that neither perforin nor IFN-γ is required for the development or expression of adaptive immunity to LM. In addition, the results suggest the potential for perforin and IFN-γ to regulate the magnitude of the CD8+ T cell response to infection.