Opposing roles for RelB and Bcl-3 in regulation of T-box expressed in T cells, GATA-3, and Th effector differentiation

CD4(+) T cells with a block in the NF-kappa B signaling pathway exhibit decreases in Th1 responses and diminished nuclear levels of multiple transactivating NF-kappa B/Rel/I kappa B proteins. To determine the lineage-intrinsic contributions of these transactivators to Th differentiation, T cells from mice deficient in specific subunits were cultured in exogenous cytokines promoting either Th1 or Th2 differentiation. Relli-deficient cells exhibited dramatic defects in Th1 differentiation and IFN-gamma production, whereas no consistent defect in either Th1 or Th2 responses was observed with c-Rel-deficient cells. In sharp contrast, Bcl-3-null T cells displayed no defect in IFN-gamma production, but their Th2 differentiation and IL-4, IL-5, and IL-13 production were significantly impaired. The absence of ROB led to a dramatic decrease in the expression of, T-box expressed in T cells and Stat4. In contrast, Bcl-3-deficient cells exhibited decreased GATA-3, consistent with evidence that Bcl-3 can transactivate a gata3 promoter. These data indicate that Bcl-3 and RelB exert distinct and opposing effects on the expression of subset-determining transcription factors, suggesting that the characteristics of Th cell responses may be regulated by titrating the stoichiometry of transactivating NF-kappa B[ReVIKB complexes in the nuclei of developing helper effector cells.