Beschreibung:
<jats:title>Abstract</jats:title><jats:p>The B cell activation antigen B7/BB1 has been shown to co‐stimulate growth of human T cells by binding the T cell molecule CD28. In mice, the heat‐stable antigen (HSA) has also been shown to act as a co‐stimulator for T cell growth. In this study, we have evaluated the contributions of B7 and HSA to the co‐stimulatory activity of antigen‐presenting cells (APC). Mouse B7 provides co‐stimulatory activity for murine CD4 T cells in anti‐CD3‐induced proliferation. Human CTLA4Ig, a chimeric molecule comprising the extracellular region of CTLA‐4 fused to an immunoglobulin Cγ fragment, binds to murine B7. We, therefore, use human CTLA4Ig and the hamster anti‐HSA monoclonal antibody 20C9 to analyze the relative contributions of B7 and HSA to the co‐stimulatory activity of murine spleen APC. Our data reveal that both murine B7 and HSA are expressed by dendritic cells and by low‐density spleen B cells. Either CTLA4Ig alone or anti‐HSA alone inhibited CD4 T cell proliferation to anti‐CD3 by > 90%, while CTLA4Ig and anti‐HSA together were far more efficient in inhibiting clonal expansion of CD4 T cells. These results demonstrate that functionally defined co‐stimulation involves at least B7 and HSA and suggest that signals delivered by B7 and HSA synergize in promoting T cell growth.</jats:p>