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A Critical Role for CD2 in Both Thymic Selection Events and Mature T Cell Function1

To examine the function of CD2 in vivo, N15 TCR transgenic (tg) RAG-2−/− H-2b mice bearing a single TCR specific for the vesicular stomatitis virus octapeptide bound to the H-2Kb 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 ∼100-fold less responsive to vesicular stomatitis virus octapeptide and unresponsive to weak peptide agonists, as judged by IFN-γ production. Repertoire analysis shows substantial differences in Vα 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.