Suppressor of cytokine signaling-1 has IFn-gamma-independent actions in T cell homeostasis
Details
Publication Year 2003-01-15, Volume 170, Issue #2, Page 878-886
Journal Title
JOURNAL OF IMMUNOLOGY
Publication Type
Journal Article
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 CD4:CD8 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-I is a critical regulator of T cell activation and homeostasis, and its influence extends beyond regulating IFN-gamma signaling.
Publisher
AMER ASSOC IMMUNOLOGISTS
Keywords
INTERFERON-GAMMA; TRANSGENIC MICE; INFLAMMATORY DISEASE; IN-VIVO; LYMPHOID HOMEOSTASIS; CUTTING EDGE; RECEPTOR; PROLIFERATION; INHIBITOR; DIFFERENTIATION
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Creation Date: 2003-01-15 12:00:00
Last Modified: 0001-01-01 12:00:00
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