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Perforin-deficient CD8+ T cells provide immunity to Listeria monocytogenes by a mechanism that is independent of CD95 and IFN-gamma but requires TNF-alpha
Journal article   Peer reviewed

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

Douglas W White and John T Harty
The Journal of immunology (1950), Vol.160(2), pp.898-905
01/15/1998
DOI: 10.4049/jimmunol.160.2.898
PMID: 9551927

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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 C57BI/6 (B6) and perforin-deficient (PO) mice to generate CD8+ T cell lines specific for the L. mono cytogenes-encoded Ag listeriolysin O (LLO). Both lines specifically produce IFN-gamma and TNF-alpha, 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-gamma-depleted hosts. However, PO-derived CD8+ T cells fail to provide antilisterial immunity in hosts depleted of TNF-alpha. 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-gamma, but requires TNF-alpha.
Cytotoxicity Tests, Immunologic Spleen - immunology CD8-Positive T-Lymphocytes - transplantation Tumor Necrosis Factor-alpha - genetics Adoptive Transfer Listeria monocytogenes - immunology Tumor Necrosis Factor-alpha - deficiency Mice, Inbred MRL lpr Bacterial Toxins Listeriosis - immunology CD8-Positive T-Lymphocytes - metabolism Pore Forming Cytotoxic Proteins fas Receptor - physiology Epitopes, T-Lymphocyte - immunology Interferon-gamma - genetics Interferon-gamma - deficiency Perforin Hemolysin Proteins Mice, Inbred C57BL Interferon-gamma - physiology Spleen - cytology Heat-Shock Proteins - immunology Membrane Glycoproteins - genetics Mice, Knockout Animals Tumor Necrosis Factor-alpha - physiology Mice CD8-Positive T-Lymphocytes - immunology Membrane Glycoproteins - deficiency Cytotoxicity, Immunologic

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