Abstract
The immune system surveys the skin for keratinocytes (KCs) infected by viruses or with acquired genetic damage. The mechanism by which T cells mediate KC elimination is however undefined. In this study we show that antigen-specific CD8 T cells can eliminate antigen-bearing KCs in vivo and inhibit their clonogenic potential in vitro, independently of the effector molecules perforin and Fas-ligand (Fas-L). In contrast, IFN-gamma receptor expression on KCs and T cells producing IFN-gamma are each necessary and sufficient for in vitro inhibition of KC clonogenic potential. Thus, antigen-specific cytotoxic T lymphocytes (CTLs) may mediate destruction of epithelium expressing non-self antigen by eliminating KCs with potential for self-renewal through an IFN-gamma-dependent mechanism.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / immunology
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology*
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Cell Communication / immunology
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Cell Division / immunology
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Cell Line
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Clone Cells / cytology
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Clone Cells / immunology
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Fas Ligand Protein / immunology
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Female
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Graft Rejection / immunology
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Interferon-gamma / genetics*
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Interferon-gamma / immunology*
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Keratinocytes / cytology
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Keratinocytes / immunology*
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Major Histocompatibility Complex / immunology
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Pore Forming Cytotoxic Proteins / immunology
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Skin / cytology*
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Skin / immunology*
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Skin Transplantation / immunology
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T-Lymphocytes, Cytotoxic / cytology
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T-Lymphocytes, Cytotoxic / immunology
Substances
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Fas Ligand Protein
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Fasl protein, mouse
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Pore Forming Cytotoxic Proteins
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perforin, mouse
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Interferon-gamma