A critical role for CD2 in both thymic selection events and mature T cell function.
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.
Sasada
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Laboratory of Immunobiology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Reinherz
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D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D018801:CD2 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018664:Interleukin-12 / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D000956:Antigens, Viral; D018801:CD2 Antigens; D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C090377:pre-T cell receptor alpha; D018664:Interleukin-12; D007371:Interferon-gamma