TGF-BETA INHIBITS IL-2-INDUCED TYROSINE PHOSPHORYLATION AND ACTIVATION OF JAK-1 AND STAT-5 IN T-LYMPHOCYTES

Signaling through IL-2R, IL-2 induces tyrosine phosphorylation and act ivation oi Jak-1 and Jak-3 kinases and Stat 3 and Stat 5 transcription factors leading to cell cycle progression of activated T cells from G (1) to S phase. TGF-beta is an immunosuppressive cytokine, which inhib its T cell proliferation at G(1) to S phase transition. We examined th e effect of TGF-beta on IL-2R signal transduction pathway in activated T cells. We show here that treatment of activated T cells with TGF-be ta inhibited IL-2-induced tyrosine phosphorylation and activation of J ak-1 and Stat 5 but not Jak-3 and Stat 3. TGF-beta also inhibited IL-2 -induced expression of alpha- and beta-chains of IL-2R and induced apo ptotic cell death in T cells. These results suggest that TGF-beta-indu ced growth arrest and apoptosis are associated with the modulation of IL-2-induced activation of)ak-Stat pathway in T cells.