Studies on the interdependence of gp39 and B7 expression and function during antigen‐specific immune responses

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Abstract
Interactions between T and B cells are dynamic and regulated by interacting 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 interdependence of gp39‐CD40 and CD28/CTLA‐B7 expression and function was studied in vitro during an antigeninduced immune response using T cells from mice expressing a transgenic T cell receptor (TCR). gp39 was induced on pigeon cytochrome c (PCC)‐transgenic T cells in the presence of antigen and antigen‐presenting cells. The antigen‐induced expression of gp39 on transgenic T cells was inhibited by antibodies to class II major histocompatibility complex, CD4 and LFA‐1, but not by CTLA‐4 Ig, anti‐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 and a more robust expression of B7‐2 on the cognate B cells. The addition of anti‐gp39 blocked the up‐regulated expression of B7‐1 and partially 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‐regulated B7‐1 and B7‐2 expression on B cells. In addition, interleukin‐4 and interferon‐γ up‐regulated B7‐2 expression on B cells. Taken together, these data demonstrate that the antigen‐induced expression of gp39 is dependent on TCR‐derived signals, yet independent of CD28/CTLA‐4 co‐stimulatory signals. Cognate interactions also resulted in the modest enhancement of B7‐1 expression and a more profound expression of B7‐2 which were completely or partially dependent on gp39‐CD40 interactions.