Abstract
The effector function of most MHC class I allospecific CTL is inhibited by anti-CD8 mAb. In the present study, we report the surprising observation that multi-valent cross-linking of CD8 molecules on precursor cells by specific antibody actively induces the generation of CD8+ class I allospecific CTL whose lytic function is resistant to anti-CD8 antibody inhibition, and actively induces down-modulation of cell surface CD8 expression on these cells. In marked contrast, bi-valent cross-linking of CD8 inhibits the generation of CD8+ CTL from precursor cells and fails to induce down-modulation of cell surface CD8 expression. These results demonstrate that CD8 can transduce net positive signals, but only when the molecule is extensively cross-linked.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / immunology*
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Antigens, Differentiation, T-Lymphocyte / immunology*
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Binding, Competitive
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CD8 Antigens
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Cross-Linking Reagents
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Histocompatibility Antigens Class I / genetics
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Immunity, Innate
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Lymphocyte Activation*
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Lymphocyte Culture Test, Mixed
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C3H
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Mice, Inbred C57BL
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Mice, Inbred DBA
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Mice, Nude
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Signal Transduction*
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Stem Cells / classification
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Stem Cells / immunology*
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Stem Cells / metabolism
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T-Lymphocytes, Cytotoxic / classification
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T-Lymphocytes, Cytotoxic / immunology*
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T-Lymphocytes, Cytotoxic / metabolism
Substances
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Antibodies, Monoclonal
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Antigens, Differentiation, T-Lymphocyte
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CD8 Antigens
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Cross-Linking Reagents
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Histocompatibility Antigens Class I