Open AccessSuppressor of Cytokine Signaling-1 Has IFN-γ-Independent Actions in T Cell Homeostasis
Author(s) -
Ann L. Cornish,
Gayle M. Davey,
Donald Metcalf,
Jared F. Purton,
Jason Corbin,
Christopher J. Greenhalgh,
Rima Darwiche,
Li Wu,
Nicos A. Nicola,
Dale I. Godfrey,
William R. Heath,
Douglas J. Hilton,
Warren S. Alexander,
Robyn Starr
Publication year - 2003
Publication title -
the journal of immunology/the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.170.2.878
Subject(s) - biology , regulator , immune system , cytokine , t cell receptor , genetically modified mouse , microbiology and biotechnology , t cell , transgene , signal transduction , cd8 , immunology , homeostasis , gene , genetics
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-1 is a critical regulator of T cell activation and homeostasis, and its influence extends beyond regulating IFN-gamma signaling.