REGULATION OF NF-KAPPA-B ACTIVATION IN T-HELPER-1 AND T-HELPER-2 CELLS

In most cell types, NF-kappa B is activated by release from a cytoplas mic inhibitor protein, I kappa B, followed by its translocation to the nucleus where it binds to the regulatory regions of many genes, inclu ding the IL-2 gene in T lymphocytes. We have previously shown by elect rophoretic mobility shift assays that nuclear extracts prepared from a ctivated, non-IL-2-producing Th2 cell clones contain significantly les s p65(RelA)-p50 NF-kappa B complexes than nuclear extracts from IL-2-p roducing Th1 and Th0 clones. We show here that Th1 and Th2 cells have similar levels of cytoplasmic p65(RelA) and p50, but TCR stimulation f ails to induce the nuclear translocation of p65(RelA) in Th2 cells. Nu clear translocation of p65(RelA) can be induced by IL-1 stimulation of Th2 cells, indicating that a basic mechanism of NF-kappa B activation common to many cells is intact in Th2 cells. We demonstrate that IL-1 and TNF induce rapid nuclear translocation of p65(RelA) in T cell clo nes, whereas TCR-induced NF-kappa B activation in Th1 cells is delayed and may be longer in duration. This suggests that the TCR pathway of NF-kappa B activation is different from the cytokine pathway. Furtherm ore, we show that Th1 and Th2 cells express different levels and/or di fferent forms of I kappa B alpha, and that cytokines, but not TCR stim uli, significantly modulate detectable levels of cytoplasmic I kappa B alpha.