Suppressor of cytokine signaling-1 has IFN-gamma-independent actions in T cell homeostasis.
J Immunol
; 170(2): 878-86, 2003 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-12517953
ABSTRACT
Suppressor of cytokine signaling (SOCS)-1 is a member of a family of proteins that negatively regulate cytokine signaling pathways. We have previously established that SOCS-1 is a key regulator of IFN-gamma signaling and that IFN-gamma is responsible for the complex inflammatory disease that leads to the death of SOCS-1-deficient mice. In this study, we provide evidence that SOCS-1 is also a critical regulator of IFN-gamma-independent immunoregulatory factors. Mice lacking both SOCS-1 and IFN-gamma, although outwardly healthy, have clear abnormalities in their immune system, including a reduced ratio of CD4CD8 T cells in lymphoid tissues and increased expression of T cell activation markers. To examine the contribution of TCR Ag specificity to these immune defects, we have generated two lines of SOCS-1-deficient mice expressing a transgenic TCR specific for an exogenous Ag, OVA (OT-I and OT-II). Although TCR transgenic SOCS-1(-/-) mice have a longer lifespan than nontransgenic SOCS-1(-/-) mice, they still die as young adults with inflammatory disease and the TCR transgenic SOCS-1(-/-) T cells appear activated despite the absence of OVA. This suggests that both Ag-dependent and -independent mechanisms contribute to the disease in SOCS-1-deficient mice. Thus, SOCS-1 is a critical regulator of T cell activation and homeostasis, and its influence extends beyond regulating IFN-gamma signaling.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Transdução de Sinais
/
Proteínas de Transporte
/
Citocinas
/
Subpopulações de Linfócitos T
/
Interferon gama
/
Homeostase
Limite:
Animals
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article