Suppressor of cytokine signaling 1 is required for the differentiation of CD4+ T cells.
Suppressor of cytokine signaling 1 (Socs1) is critical for the regulation of interferon-gamma responses and T cell homeostasis. Although the presentation of the inflammatory disease of Socs1-deficient mice is complex, we have tested here the hypothesis that it originates from inappropriate T cell development and the appearance of autoreactive T cells. Socs1-deficient T cell receptor-transgenic mice showed severely impaired positive selection and a substantial alteration in CD4-CD8 T cell fate specification. These defects were dependent on interferon-gamma. Moreover, negative selection was also impaired, suggesting that autoimmunity contributes to the disease observed in Socs1(-/-) mice. We conclude that the constitutive expression of Socs1 in the thymus protects the process of thymic development and selection from the effects of systemic inflammation.
Catlett
Ian M
IM
The University of California San Diego, La Jolla, California 92093-0377, USA.
Hedrick
Stephen M
SM
D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D018398:Homeodomain Proteins / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011828:Radiation Chimera; D012097:Repressor Proteins / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D002352:Carrier Proteins; D000949:Histocompatibility Antigens Class II; D018398:Homeodomain Proteins; C024138:I-E-antigen; D012097:Repressor Proteins; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C064658:RAG-1 protein; D007371:Interferon-gamma