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Adaptive immunity and enhanced CD8+ T cell response to Listeria monocytogenes in the absence of perforin and IFN-gamma
Journal article   Peer reviewed

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

V P Badovinac and J T Harty
The Journal of immunology (1950), Vol.164(12), pp.6444-6452
06/15/2000
DOI: 10.4049/jimmunol.164.12.6444
PMID: 10843700

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Abstract

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 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 approximately 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.
T-Lymphocyte Subsets - immunology CD8-Positive T-Lymphocytes - transplantation Immunity, Innate - genetics Listeria monocytogenes - immunology Bacterial Toxins Listeriosis - immunology CD8-Positive T-Lymphocytes - metabolism Bacterial Proteins - immunology Pore Forming Cytotoxic Proteins fas Receptor - physiology Epitopes, T-Lymphocyte - immunology Interferon-gamma - genetics Interferon-gamma - deficiency Perforin Cell Line Cytotoxicity, Immunologic - genetics Genetic Predisposition to Disease Hemolysin Proteins Listeriosis - genetics Membrane Proteins - genetics Bacterial Proteins - genetics Membrane Proteins - immunology Heat-Shock Proteins - immunology Membrane Glycoproteins - genetics Mice, Knockout Listeria monocytogenes - pathogenicity Animals Virulence - immunology Listeria monocytogenes - genetics Listeriosis - microbiology Mice Mice, Inbred BALB C CD8-Positive T-Lymphocytes - immunology Tumor Necrosis Factor-alpha - biosynthesis Membrane Glycoproteins - deficiency

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