Cutting edge: TCR stimulation by antibody and bacterial superantigen induces Stat3 activation in human T cells

Recent data show that TCR/CD3 stimulation induces activation of Stat5 in mu rine T cells, Here, we show that CD3 ligation by mAb and Staphylococcal ent erotoxin (SE) induce a rapid, gradually accumulating, long-lasting tyrosine , and serine phosphorylation of Stall (but not Stat5) in allogen-specific h uman CD4(+) T cell lines. In contrast, IL-2 induces a rapid and transient t yrosine and serine phosphorylation of Stat3, Compared with IL-2, CD3 ligati on induces a delayed Stat3 binding to oligonucleotide probes from the ICAM- 1 and IL-2R alpha promoter. CD3-mediated activation of Stat3 is almost comp letely inhibited by a Src kinase inhibitor (PP1), whereas IL-2-induced Stat 3 activation is unaffected. In conclusion, we show that CD3 ligation by mAb and SE triggers a rapid, PP1-sensitive tyrosine and serine phosphorylation of Stat3 in human CD4(+) T cells, Moreover, we provide evidence that TCR/C D3 and IL-2 induce Stat3 activation via distinct signaling pathways.