INTERLEUKIN-2 AND INTERLEUKIN-15 ACTIVATE STAT3-ALPHA IN HUMAN T-LYMPHOCYTES

Signal transducer and activator of transcription 3 (Stat3) has recentl y been shown to exist in two alternatively spliced isoforms, a short f orm, Stat3 beta, and a longer form, Stat3 alpha, displaying difference s in transcriptional activity, It is unknown which Stat3 isoform(s) is activated in response to interleukin (IL)-2 and IL-15, Here, cytokine -induced activation of Stat3 in previously activated CD4(+) human T ce lls was examined using Stat3 antibodies directed against different reg ions of Stat3. As determined by tyrosine phosphorylation, nuclear tran slocation and binding to an hSIE-oligonucleotide probe, IL-2 and IL-15 activated the slowly migrating isoform, Stat3 alpha. In contrast, min imal or no activation of Stat3 beta was observed, suggesting that IL-2 and IL-15 predominantly activate Stat3 alpha in human CD4(+) T cells. In this way, diversity in the expression and activation of Stat3 prot eins may provide additional means of regulating cytokine-induced T cel l responses. (C) 1998 Academic Press.