Differential effects of B7-1 and B7-2 on the costimulation of mouse nonspecific cytotoxic T lymphocyte development in response to anti-CD3 antibody

Despite extensive study, the relative contribution of B7-1 and B7-2 molecul es to the costimulation of cytotoxic T lymphocyte (CTL) activation remains controversial. We used blocking mAbs to B7-1 and B7-2 molecules to determin e the role of these B7 family members ill the in vitro induction of mouse n onspecific CTL in response to soluble anti-CD3 mAb, Optimal induction of an ti-CD3-activated killer-T (AK-T) cells Teas found to require interactions,v ith B7-2 on residual accessory cells in nylon wool-nonadherent spleen cell preparations during the first 12 h of culture in the presence of anti-CD3 m Ab, Because B7-1 is not expressed at high enough levels on residual accesso ry cells in primary T cell cultures to be an effective Ligand for CD28, we used LPS-stimulated B cells, which express substantial B7-1, in addition to B7-2, to determine the contribution of B7-1 to AK-T cell development, Comp ared with B7-2, the contribution of B7-1 to the costimulation of AK-T cells in this system Tvas modest because anti-B7-1 mAb had only a minimal inhibi tory effect on the generation of cytotoxicity, whereas anti-B7-2 mAb strong ly inhibited AIC-T cell development. Anti-CDS-induced cytotoxicity of T cel ls from CD4 knockout mice and CD4-depleted nylon wool-nonadherent spleen ce lls from wild-type mice was inhibited by anti-B7-2 mAb, implying that B7-2 is able to bind directly to CD28 on CD8(+) T cells lid costimulate their ac tivation, B7-1 blockade, on the other hand, did not affect the costimulatio n of CD8(+) T cells. Blockade of B7-2/ CD28 interactions with anti-B7-2 mAb strongly inhibited granzyme B, but not perforin or Fas ligand gene express ion, suggesting an explanation for the inhibitory effect of anti-B7-2 mAb o n AK-T cell development. These data indicate that B7-2 is superior to B7-1 as a costimulator of mouse AK-T cell induction.