Abstract
To examine the function of CD2 in vivo, N15 TCR transgenic (tg) RAG-2(-/-) H-2(b) mice bearing a single TCR specific for the vesicular stomatitis virus octapeptide bound to the H-2K(b) molecule were compared on a wild-type or CD2(-/-) background. In N15tg RAG-2(-/-) CD2(-/-) mice, thymic dysfunction is evident by 6 wk with a pre-TCR block in the CD4(-)CD8(-) double-negative thymocytes at the CD25(+)CD44(-) stage. Moreover, mature N15tg RAG-2(-/-) CD2(-/-) T cells are approximately 100-fold less responsive to vesicular stomatitis virus octapeptide and unresponsive to weak peptide agonists, as judged by IFN-gamma production. Repertoire analysis shows substantial differences in Valpha usage between non-tg C57BL/6 (B6) and B6 CD2(-/-) mice. Collectively, these findings show that CD2 plays a role in pre-TCR function in double-negative thymocytes, TCR selection events during thymocyte development, and TCR-stimulated cytokine production in mature T cells.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, Viral / immunology
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CD2 Antigens / biosynthesis
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CD2 Antigens / genetics
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CD2 Antigens / physiology*
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cytotoxicity, Immunologic / genetics
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Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
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Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
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Immunophenotyping
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Interferon-gamma / antagonists & inhibitors
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Interferon-gamma / biosynthesis
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Interleukin-12 / physiology
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Killer Cells, Natural / immunology
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Lymphocyte Activation / genetics
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Lymphocyte Count
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Lymphopenia / genetics
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Lymphopenia / immunology
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Lymphopenia / pathology
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Receptors, Antigen, T-Cell, alpha-beta / deficiency
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Signal Transduction / genetics
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Signal Transduction / immunology
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Spleen / immunology
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Spleen / pathology
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T-Lymphocyte Subsets / cytology*
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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T-Lymphocyte Subsets / pathology
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T-Lymphocytes, Cytotoxic / immunology
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Thymus Gland / cytology*
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Thymus Gland / immunology*
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Thymus Gland / metabolism
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Thymus Gland / pathology
Substances
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Antigens, Viral
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CD2 Antigens
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Membrane Glycoproteins
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Receptors, Antigen, T-Cell, alpha-beta
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pre-T cell receptor alpha
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Interleukin-12
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Interferon-gamma