title: Loss of interferon-induced Stat1 phosphorylation in activated T cells.
abstract: Modulation of cytokine responsiveness following T cell activation represents an important mechanism that shapes the fate of T cells after encounters with antigens. We activated T cells in mice with superantigen and assessed their ability to phosphorylate Stat1 in response to interferon-gamma (IFN-gamma) and IFN-alpha. After 4 h of activation in vivo, T cells became deficient in their ability to phosphorylate Stat1 in response to either cytokine. The loss of IFN sensitivity was accompanied by increased mRNA transcription for multiple suppressors of cytokine signaling (SOCS) genes (SOCS1, SOCS3, and SOCS7). The transcript levels of these SOCS were elevated only during the early hours after activation and were at or below normal levels by 60 h. Likewise, the activation-induced inhibition of IFN-alpha signaling was transient, and sensitivity was restored by 3 days postactivation. The loss of sensitivity to IFN-gamma persisted, however, and was still evident at 3 days. These data suggest that SOCS-independent mechanisms specific for inhibition of IFN-gamma signaling may be present at later stages of the T cell response. The loss of Stat1 signaling may be a factor in differentiation of T cells during and after activation, and it could also represent a protective mechanism against the toxic effects of IFN-gamma during immune responses.
authors.affiliation: Department of Surgery, University of Oklahoma College of Medicine, Tulsa, OK 74135, USA.
authors.forename: C Justin
authors.initials: CJ
authors.lastname: Van De Wiele
authors.forename: Julie H
authors.initials: JH
authors.lastname: Marino
authors.forename: Michael E
authors.initials: ME
authors.lastname: Whetsell
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Vo
authors.forename: Rhonda M
authors.initials: RM
authors.lastname: Masengale
authors.forename: T Kent
authors.initials: TK
authors.lastname: Teague
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D018106:CD28 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004768:Enterotoxins / Q000276:immunology; D005260:Female; D016898:Interferon-alpha / Q000037:antagonists & inhibitors / Q000235:genetics; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000235:genetics; D007372:Interferons / Q000037:antagonists & inhibitors* / Q000235:genetics; D053613:Janus Kinase 1; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D017471:Receptors, Interferon / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D013601:T-Lymphocytes / Q000276:immunology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D000096743:Interferon gamma Receptor
chemical_list: D000906:Antibodies; D018106:CD28 Antigens; D017252:CD3 Complex; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D004768:Enterotoxins; D016898:Interferon-alpha; D007371:Interferon-gamma; D007372:Interferons; D053613:Janus Kinase 1; D011505:Protein-Tyrosine Kinases; D012333:RNA, Messenger; D017471:Receptors, Interferon; D012097:Repressor Proteins; D050794:STAT1 Transcription Factor; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000096743:Interferon gamma Receptor; C491590:Socs1 protein, mouse; C491411:Socs3 protein, mouse; C494080:Stat1 protein, mouse; C031818:enterotoxin B, staphylococcal; C507905:Jak1 protein, mouse