Highly purified populations of dendritic cells (DCs) can be isolated from various tissues such as skin and blood. These sites are likely to encounter secreted toxins of bacteria such as super-antigens. In vivo, DCs express the cell surface molecule B7, a counterreceptor for CD28 which provides costimulation to resting T cells. Highly purified preparations of DCs obtained from the epidermis and dermis of normal skin as well as blood were used to study the role of B7 in superantigen presentation to autologous T cells, as well as in alloantigen responses. We compared these results to those obtained with nondendritic antigen presenting cells (APCs) such as mono-nuclear cells derived from the Ficoll-Hypaque interface (PBMCs). All DC populations strongly express B7, and in a purely autologous system staphylococcal enterotoxin B (SEB)-mediated T cell proliferation was inhibited by 55-85% using a soluble chimeric fusion protein (i.e., CTLA41g), a potent inhibitor of CD28:B7 interaction. In contrast, while T cells also proliferated vigorously when stimulated by SEB in the presence of autologous PBMC (which only weakly express B7), costimulation was not inhibited by CTLA41g. In allogeneic responses, Dcs were also more potent stimulators compared to PBMC, but both types or APC:T cell reactions were almost completely inhibited by CTLA41g (>90%). For both SEB-mediated reactions and alloantigen reactions, the relative importance of LFA-1 and HLA-DR was similar between Dcs and PBMCs. The data indicate that these Dcs express B7, which can function in the SEB-driven response of autologous T cells, as well as in allogeneic T cell reactions. Overall, when comparing the relative costimulatory capabilities of different types of APCs, it appears the relatively low level of B7 expressed by PBMC functioned effectively in allogeneic reactions, whereas only the higher levels of B7 expressed by these DC populations functioned in SEB-mediated T cell responses.