CD80 (B7) AND CD86 (B70) PROVIDE SIMILAR COSTIMULATORY SIGNALS FOR T-CELL PROLIFERATION, CYTOKINE PRODUCTION, AND GENERATION OF CTL

Signals initiated through both the TCR complex and CD28 are required f or optimal activation of T lymphocytes. Recently, it has been demonstr ated that CD28 interacts with two different ligands, designated CD80 ( B7/B7-1) and CD86 (B70/B7-2). We have produced stable transfectants th at express CD80, CD86, or both ligands and have examined their ability to costimulate T cell proliferation, cytokine production, and the gen eration of CTL. When we used small, resting human peripheral blood T c ells as responders, both CD80 and CD86 transfectants efficiently costi mulated anti-CD3 mAb-induced proliferation and the secretion of IL-2 a nd IFN-gamma. Additionally, both CD80 and CD86 transfectants were able to generate functional CTL. The magnitude and kinetics of these respo nses were similar, which indicates that both ligands provide efficient costimulatory signals. Because many APCs coexpress both CD80 and CD86 , we compared the ability of anti-CD80 and anti-CD86 mAbs to inhibit a llogeneic MLR stimulated with B lymphoblastoid cell lines and showed t hat it is necessary to inhibit interactions with both ligands to optim ally block CD28-dependent proliferation. Given the limited homology of CD80 and CD86, it was surprising that the binding of CD28-Ig fusion p rotein to CD80 and that to CD86 transfectants were essentially indisti nguishable. Binding of CTLA-4-Ig fusion protein to both transfectants also was quite similar, but was of higher affinity than CD28-Ig bindin g. Results from these studies indicate that both CD80 and CD86 are pot ent and similar costimulators of T lymphocytes. Therefore, the role of CD80 and CD86 in an immune response may be determined primarily by th eir differential expression on APC.