title: 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).
abstract: Staphylococcal enterotoxins (SE) stimulate T cells expressing the appropriate variable region beta chain of (V beta) 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 SEB, 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 IL2R alpha and IL2R 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.
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004768:Enterotoxins / Q000494:pharmacology*; D006801:Humans; D053616:Janus Kinase 3; D008213:Lymphocyte Activation / Q000187:drug effects; D046911:Macromolecular Substances; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000378:metabolism*; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects; D018089:Superantigens / Q000494:pharmacology; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D004768:Enterotoxins; D046911:Macromolecular Substances; D015375:Receptors, Interleukin-2; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D018089:Superantigens; D015534:Trans-Activators; D019000:Phosphotyrosine; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3