B7‐1‐dependent co‐stimulation results in qualitatively and quantitatively different responses by CD4+ and CD8+ T cells

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Abstract
To characterize better the co‐stimulatory activity of native B7‐1 in the absence of other receptor/ligand interactions that might contribute to the response, B7‐1 was purified by monoclonal antibody (mAb) affinity chromatography. Immobilization of purified B7‐1 with anti‐T cell receptor (TCR) mAb on cell‐sized latex microspheres provided an effective stimulus for activation of both CD4+ and CD8+ T cells as measured by proliferation, development of effector function, and changes in motility and adhesion. The CD4+ T cell response was prolonged and resulted in efficient interleukin‐2 production and clonal expansion. In contrast, CD8+ responses were transient. Proliferation and clonal expansion peaked on days 3 and 4, coincident with maximal expression of lytic effector function, and the cells then died. These results demonstrate that B7‐1 mediated co‐stimulation is sufficient for the induction of effector function in both helper and cytotoxic T cell precursors, but suggest that B7‐1 co‐stimulation is not sufficient to sustain helper‐independent CD8+ CTL responses. When the dose responses of CD4+ and CD8+ T cells to B7‐1 were compared, CD8+ T cells were found to require higher densities of B7‐1 to attain an equivalent level of activation, suggesting that the level of expression of B7‐1 by APC may influence the development of helper or CTL responses. Finally, in contrast to results obtained by others with B7‐1 transfectants, purified B7‐1 did not provide co‐stimulation when presented on a surface separate from the TCR stimulus.