Costimulation light: Activation of CD4(+) T cells with CD80 or CD86 ratherthan anti-CD28 leads to a Th2 cytokine profile

To examine the role of CD28 and CTLA-4 in Th cell differentiation, we used a novel microsphere-based system to compare the effects of CD28 ligation by Ab or CD80/CD86. One set of beads was prepared by coating,vith anti-CD3 an d anti-CD28 Ab, Another set of beads was prepared by immobilizing anti-CD3 and murine CD80-Ig fusion protein or murine CD86-Ig fusion protein on the b eads. The three sets of beads were compared in their effects on the ability to activate and differentiate splenic CD4 T cells. When purified naive CD4 (+) cells were stimulated in vitro, robust proliferation of similar magnitu de was induced by all three sets of beads. When cytokine secretion was exam ined, all bead preparations induced an equivalent accumulation of IL-2, In contrast, there was a marked difference in the cytokine secretion pattern o f the Th2 cytokines IL-4, IL-10, and IL-13, The B7-Ig-stimulated cultures h ad high concentrations of Th2 cytokines, whereas there were low or undetect able concentrations in the anti-CD28-stimulated cultures. Addition of anti- CTLA-4 Fab augmented B7-mediated IL-4 secretion, These studies demonstrate that B7 is a critical and potent stimulator of Th2 differentiation, and tha t anti-CD28 prevents this effect.