STUDIES ON THE INTERDEPENDENCE OF GP39 AND B7 EXPRESSION AND FUNCTIONDURING ANTIGEN-SPECIFIC IMMUNE-RESPONSES

Interactions between T and B cells are dynamic and regulated by intera cting receptor: co-receptors. Interactions between CD40 and its ligand , gp39, and the CD28/CTLA-4 and B7 family members play a decisive role in regulating the progression of cognate interactions. The interdepen dence of gp39-CD40 and CD28/CTLA-B7 expression and function was studie d in vitro during an antigen-induced immune response using T cells fro m mice expressing a transgenic T cell receptor (TCR). gp39 was induced on pigeon cytochrome c (PCC)-transgenic T cells in the presence of an tigen and antigen-presenting cells. The antigen-induced expression of gp39 on transgenic T cells was inhibited by antibodies to class II maj or histocompatibility complex, CD4 and LFA-1, but not by CTLA-4 Ig, an ti-B7-1 or anti-B7-2. These data established that the antigen-induced expression of gp39 was not dependent on co-stimulation via CD28/CTLA-4 . The addition of PCC also resulted in the modest expression of B7-1 a nd a more robust expression of B7-2 on the cognate B cells. The additi on of anti-gp39 blocked the up-regulated expression of B7-1 and partia lly blocked the up-regulated expression of B7-2. The addition of anti- gp39 and anti-interleukin-4 inhibited antigen-induced expression of B7 -2 on B cells to near background levels. Studies on the up-regulation of B7-1 and B7-2 on resting B cells showed that soluble gp39 up-regula ted B7-1 and B7-2 expression on B cells. In addition, interleukin-4 an d interferon-gamma up-regulated B7-2 expression on B cells. Taken toge ther, these data demonstrate that the antigen-induced expression of gp 39 is dependent on TCR-derived signals, yet independent of CD28/CTLA-4 co-stimulatory signals. Cognate interactions also resulted in the mod est enhancement of B7-1 expression and a more profound expression of B 7-2 which were completely or partially dependent on gp39-CD40 interact ions.