STAPHYLOCOCCAL ENTEROTOXINS MODULATE INTERLEUKIN 2 RECEPTOR EXPRESSION AND LIGAND-INDUCED TYROSINE PHOSPHORYLATION OF THE JANUS PROTEIN-TYROSINE KINASE 3 (JAK3) AND SIGNAL TRANSDUCERS AND ACTIVATORS OF TRANSCRIPTION (STAT PROTEINS)

摘要

Staphylococcal enterotoxins (SE) stimulate T cells expressing the appropriate variable region beta chain df (V(b)eta) T-cell receptors and have been implicated in the pathogenesis of several autoimmune diseases. Depending on costimulatory signals, SE induce either proliferation or anergy in T cells. In addition, SE can induce an interleukin-2 (IL-2) nonresponsive state and apoptosis. Here, we show that SE induce dynamic changes in the expression of and signal transduction through the IL-2 receptor (IL-2R) beta and gamma chains (IL-2R beta and IL-2R gamma) in human antigen-specific CD4(+) T-cell lines. Thus, after 4 hr of exposure to SEA and SEE, the expression of IL-2R beta was down-regulated, IL-2R gamma was slightly up-regulated, while IL-2R alpha remained largely unaffected. The changes in the composition of IL-2Rs were accompanied by inhibition of IL-2-induced tyrosine phosphorylation of the Janus protein-tyrosine kinase 3 (Jak3) and signal transducers and activators of transcription called Stat3 and Stat5. In parallel experiments, IL-2-driven proliferation was inhibited significantly. After 16 hr of exposure to SE, the expression of IL-2R beta remained low while that of IL-2R alpha and IL-2R gamma was further up-regulated, and ligand-induced tyrosine phosphorylation of Jak3 and Stat proteins was partly normalized. Yet, IL-2-driven proliferation remained profoundly inhibited, suggesting that signaling events other than Jak3/Stat activation had also been changed following SE stimulation. In conclusion, our data suggest that SE can modulate IL-2R expression and signal transduction involving the Jak/Stat pathway in CD4(+) T-cell lines. [References: 49]