B7-2 (CD86) IS ESSENTIAL FOR THE DEVELOPMENT OF IL-4-PRODUCING T-CELLS

The CD28/CTLA-4 ligands, B7-1 (CD80) and B7-2 (CD86), provide a co-sti mulatory signal necessary for optimal T cell activation. We have exami ned the effect of blocking B7-1 and B7-2 in an in vitro system using o valbumin-specific T cells from alpha beta TCR-transgenic mice. This sy stem allowed us to examine the interaction of B7 co-stimulators on phy siologic antigen-presenting cells (APC) with antigen-specific T helper precursor (T(h)p) cells. We report that blocking T(h)p/B7-1 or B7-2 i nteractions in a primary response differentially affects the cytokine profile observed in a secondary stimulation, even in the absence of ad ditional anti-B7 antibody, Engagement of B7-2 in the primary stimulati on was found to be essential for production of the T(h)2 cytokine, IL- 4, but not the T(h)1 cytokines, IL-2 and IFN-gamma, in a secondary sti mulation. Conversely, inclusion of the anti-B7-1 mAb in cultures using highly purified naive T cells increased levels of IL-4 and significan tly 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-linkin g, as F(ab) fragments mimicked the intact antibody, Taken together, ou r data demonstrate that the interaction between T(h)p and B7-2 favors the development of T(h)2 cells.