B7-2 (CD86) is essential for the development of IL-4-producing T cells

Abstract

The CD28/CTLA-4 ligands, B7-1 (CD80) and B7-2 (CD86), provide a co-stimulatory signal necessary for optimal T cell activation. We have examined the effect of blocking B7-1 and B7-2 in an in vitro system using ovalbumin-specific T cells from alpha beta TCR-transgenic mice. This system allowed us to examine the interaction of B7 co-stimulators on physiologic antigen-presenting cells (APC) with antigen-specific T helper precursor (ThP) cells. We report that blocking Thp/B7-1 or B7-2 interactions in a primary response differentially affects the cytokine profile observed in a secondary stimulation, even in the absence of additional anti-B7 antibody. Engagement of B7-2 in the primary stimulation was found to be essential for production of the Th2 cytokine, IL-4, but not the Th1 cytokines, IL-2 and IFN-gamma, in a secondary stimulation. Conversely, inclusion of the anti-B7-1 mAb in cultures using highly purified naive T cells increased levels of IL-4 and significantly depressed levels of IFN-gamma, upon re-stimulation. The effect of the anti-B7-2 mAb in reducing IL-4 production could be overcome by the addition of recombinant IL-4 in the primary stimulation. The effects of the anti-B7-2 mAb appear to be due to blocking and not cross-linking, as F(ab) fragments mimicked the intact antibody. Taken together, our data demonstrate that the interaction between Thp and B7-2 favors the development of Th2 cells.