Abstract
In analyzing mechanisms of protection against intracellular infections, a series of human CD1-restricted T cell lines of two distinct phenotypes were derived. Both CD4(-)CD8(-) (double-negative) T cells and CD8(+) T cells efficiently lysed macrophages infected with Mycobacterium tuberculosis. The cytotoxicity of CD4(-)CD8(-) T cells was mediated by Fas-FasL interaction and had no effect on the viability of the mycobacteria. The CD8(+) T cells lysed infected macrophages by a Fas-independent, granule-dependent mechanism that resulted in killing of bacteria. These data indicate that two phenotypically distinct subsets of human cytolytic T lymphocytes use different mechanisms to kill infected cells and contribute in different ways to host defense against intracellular infection.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antigens, CD1 / immunology*
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Cell Line
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Coculture Techniques
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Colony Count, Microbial
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Cytoplasmic Granules / immunology
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Cytotoxicity, Immunologic*
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Fas Ligand Protein
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Granzymes
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Humans
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Lymphocyte Activation
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Macrophages / immunology*
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Macrophages / microbiology
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / immunology
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Membrane Glycoproteins / metabolism
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Mycobacterium tuberculosis / growth & development
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Mycobacterium tuberculosis / immunology*
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Perforin
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Phenotype
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Pore Forming Cytotoxic Proteins
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Serine Endopeptidases / metabolism
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Strontium / pharmacology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocytes, Cytotoxic / immunology*
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fas Receptor / immunology
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fas Receptor / metabolism
Substances
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Antigens, CD1
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FASLG protein, human
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Fas Ligand Protein
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Membrane Glycoproteins
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Pore Forming Cytotoxic Proteins
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fas Receptor
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Perforin
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Granzymes
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Serine Endopeptidases
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GZMA protein, human
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Strontium