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 viru s 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 negativ e thymocytes at the CD25+CD44- stage. Moreover, mature N15tg RAG-2(-/-) CD2 (-/-) T cells are similar to 100-fold less responsive to vesicular `stomati tis virus octapeptide and unresponsive to weak peptide agonists, as judged by IFN-gamma production. Repertoire analysis shows substantial differences in V alpha usage between non-tg C57BL/6 (B6) and B6 CD2(-/-) mice. Collecti vely, these findings show that CD2 plays a role in pre-TCR function in doub le-negative thymocytes, TCR selection events during thymocyte development, and TCR-stimulated cytokine production in mature T cells. The Journal of Im munology, 2001, 166: 2394-2403.