REGULATION OF T-HELPER CELL-DIFFERENTIATION IN-VIVO BY SOLUBLE AND MEMBRANE-PROTEINS PROVIDED BY ANTIGEN-PRESENTING CELLS

The aim of this study was to Lest whether the nature of the antigen-pr esenting cell (APC) can influence the Th1/Th2 balance in vivo. Our dat a show that dendritic cells (DC), pulsed extracorporeally with antigen , induced the development of cells secreting IL-2, IFN-gamma and IL-4 upon antigen rechallenge in vitro. Priming with peritoneal macrophages sensitized cells that produced IL-4 but not IFN-gamma. To identify th e factors involved in T helper development, mice were primed with APC with or without treatment with neutralizing antibodies to costimulator y molecules or cytokines. Our results indicate that priming with DC or macrophages is strictly dependent on the CD28-CTLA4/B7 interaction. O f note, CD86 provides the initial signal to induce naive T cells to be come IL-4 producers, whereas CD80 is a more neutral differentiation si gnal. IL-12, released by the DC, appears as a potent and obligatory in ducer of differentiation for IFN-gamma-producing cells. IL-6, although produced by both APC populations, is necessary to direct activation o f the Th2-type response by macrophages but not by DC.