STAT3 ACTIVATION IS RESPONSIBLE FOR IL-6-DEPENDENT T-CELL PROLIFERATION THROUGH PREVENTING APOPTOSIS - GENERATION AND CHARACTERIZATION OF T-CELL-SPECIFIC STAT3-DEFICIENT MICE

Stat3 a member of STAT, is activated by a variety of cytokines such as IL-6 family of cytokines, granulocyte CSF, epidermal growth factor, a nd leptin, A recent study with mice genetically deficient in the Stat3 gene has revealed its important role in the early embryogenesis. To a ssess the function of Stat3 in adult tissues, we disrupted the Stat3 g ene specifically in T cells by conditional gene targeting using Cre-Io xP system. In Stat3-deficient T cells, IL-6-induced proliferation was severely impaired, IL-6 did not enhance cell cycle progression, but pr evented apoptosis of normal T cells. In contrast, IL-6 did nut prevent apoptosis of Stat3-deficient T cells. Antiapoptotic protein, Bcl-2, w as normally up-regulated in response to IL-6 even in Stat3-deficient T cells. These results demonstrate that Stat3 activation is involved in IL-6-dependent T cell proliferation through prevention of apoptosis i ndependently of Bcl-2.