Adaptive immunity and enhanced CD8+ T cell response to Listeria monocytogenes in the absence of perforin and IFN-γ

Single Ag-specific CD8(+) T cells from IFN-gamma-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-gamma as CD8(+) T cell effector mechanisms, we generated perforin/IFN gamma (PKO/GKO) double deficient mice. PKO/GKO-derived CDS' 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 similar to 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-gamma is required for the development or expression of adaptive immunity to LM, In addition, the results suggest the potential for perforin and IFN-gamma to regulate the magnitude of the CD8(+) T cell response to infection.