B7-1-DEPENDENT CO-STIMULATION RESULTS IN QUALITATIVELY AND QUANTITATIVELY DIFFERENT RESPONSES BY CD4(-CELLS() AND CD8(+) T)

To characterize better the co-stimulatory activity of native B7-1 in t he absence of other receptor/ligand interactions that might contribute to the response, B7-1 was purified by monoclonal antibody (mAb) affin ity chromatography. Immobilization of purified B7-1 with anti-T cell r eceptor (TCR) mAb on cell-sized latex microspheres provided an effecti ve stimulus for activation of both CD4(+) and CD8(+) T cells as measur ed by proliferation, development of effector function, and changes in motility and adhesion. The CD4(+) T cell response was prolonged and re sulted in efficient interleukin-2 production and clonal expansion. In contrast, CD8(+) responses were transient. Proliferation and clonal ex pansion peaked on days 3 and 4, coincident with maximal expression of lytic effector function, and the cells then died. These results demons trate that B7-1 mediated costimulation 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 help er-independent CD8(+) CTL responses. When the dose responses of CD4(+) and CD8(+) T cells to B7-1 were compared, CD8(+) T cells were found t o require higher densities of B7-1 to attain an equivalent level of ac tivation, suggesting that the level of expression of B7-1 by APC may i nfluence the development of helper or CTL responses. Finally, in contr ast 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.