TCR-STIMULATED NAIVE HUMAN CD4(-) T-CELLS DEVELOP INTO EFFECTOR-CELLSTHAT SECRETE IL-13, IL-5, AND IFN-GAMMA, BUT NO IL-4, AND HELP EFFICIENT IGE PRODUCTION BY B-CELLS()45R0()

It is currently believed that IgE production by B cells is induced by activated CD4(+) Th2-like cells that produce increased amounts of IL-4 but low levels of IFN-gamma. We found that ''naive'' CD4(+)45RO(-) T cells primed and restimulated in vitro via the TCR developed into effe ctor cells that produced large amounts of IL-13, IL-5, and IFN-gamma, but no IL-4. Such CD4 T cells induced surface IgD(+)E(-) B cells to pr oduce large amounts of IgE. The IgE response could be blocked complete ly by neutralizing anti-IL-13 Abs, whereas anti-IL-4 had no effect. Ad dition of exogenous IL-4 during priming of CD4 cells suppressed clonal expansion and the development of Th cells including helpers for IgE, but increased endogenous production of IL-3 and IL-5, and suppressed p roduction of IFN-gamma. Addition of exogenous IFN-alpha, IFN-gamma, or neutralizing anti-IFN-gamma mAbs affected neither priming of CD4 T ce lls nor B cell help. In contrast to CD4(+)45RO(-) naive T cells, CD4()45RO(+) ''memory'' T cells primed and restimulated in vitro secreted IL-3 in addition to IL-13, IL-5, and IFN-gamma, and the IgE response i nduced by such cells could be blocked only by a combination of anti-IL -4 plus anti-IL-13 Abs. Unlike CD4 cells, CD8 cells could not be prime d to help IgE production. The results indicate that TCR/CD3 cross-link ing on naive human CD4 T cells is sufficient to induce the development of potent IgE helper cells, which secrete large amounts of IL-13, IL- 5, and IFN-gamma, but no IL-4. Such Th cells may exacerbate atopic inf lammation, because all by themselves they could drive IL-13-dependent IgE production, IL-5-dependent eosinophilia, and IFN-gamma-dependent m acrophage activation, but could not suppress IFN-gamma production by o ther T cells via IL-4.