ROLE OF COSTIMULATORS IN T-CELL DIFFERENTIATION - STUDIES USING ANTIGEN-PRESENTING CELLS LACKING EXPRESSION OF CD80 OR CD86

For T cells to be optimally activated, recognition of Ag/MHC complexes by the TCR must be accompanied by a second, costimulatory signal that can be provided efficiently by the related costimulatory molecules CD 80 (B7-1) and CD86 (B7-2). Recently, CD80 and CD86 have been implicate d as differential determinants of Th1- vs Th2-type cytokine profiles. However, this remains a controversial issue since conflicting results have been obtained in different experimental models both in vivo and i n vitro. To investigate the role of CD80 and CD86 in Th subset differe ntiation, we have examined the cytokine profiles induced in TCR transg enic T cells stimulated by peptide in association with splenic APCs ob tained from knockout mice that selectively lack expression of either t he CD80 or the CD86 molecule. Our data suggest that CD86, and to a les ser extent CD80, can make significant contributions to the production of both IL-4 and IFN-gamma. However, neither molecule plays an obligat ory role in priming for the production of either effector cytokine. Fu rthermore, CD80 and CD86 contribute to the magnitude of T cell activat ion, but do not appear to selectively regulate Th1 vs Th2 differentiat ion.