Perforin-deficient CD8+ T cells provide immunity to Listeria monocytogenes by a mechanism that is independent of CD95 and IFN-γ but requires TNF-α

DW White, JT Harty - The Journal of Immunology, 1998 - journals.aai.org
The Journal of Immunology, 1998journals.aai.org
CD8+ T cells are effective mediators of immunity against Listeria monocytogenes, but the
mechanisms by which they provide antilisterial immunity are poorly understood. CD8+ T
cells efficiently lyse target cells in vitro by at least two independent pathways. To test the
hypothesis that CD8+ T cell-mediated immunity to L. monocytogenes is dependent on
perforin or CD95 (Fas, Apo-1), we used C57Bl/6 (B6) and perforin-deficient (PO) mice to
generate CD8+ T cell lines specific for the L. monocytogenes-encoded Ag listeriolysin O …
Abstract
CD8+ T cells are effective mediators of immunity against Listeria monocytogenes, but the mechanisms by which they provide antilisterial immunity are poorly understood. CD8+ T cells efficiently lyse target cells in vitro by at least two independent pathways. To test the hypothesis that CD8+ T cell-mediated immunity to L. monocytogenes is dependent on perforin or CD95 (Fas, Apo-1), we used C57Bl/6 (B6) and perforin-deficient (PO) mice to generate CD8+ T cell lines specific for the L. monocytogenes-encoded Ag listeriolysin O (LLO). Both lines specifically produce IFN-γ and TNF-α, and mediate target cell lysis in vitro. Cytolysis mediated by the PO-derived CD8+ T cell line is delayed relative to the B6-derived line and is completely inhibited by anti-CD95 Abs. In vivo, PO-derived CD8+ T cells provide specific antilisterial immunity in B6 hosts, CD95-deficient hosts, and IFN-γ-depleted hosts. However, PO-derived CD8+ T cells fail to provide antilisterial immunity in hosts depleted of TNF-α. These results indicate that single Ag-specific CD8+ T cells derived from PO mice can mediate antilisterial immunity by a mechanism that is independent of CD95 or IFN-γ, but requires TNF-α.
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