Suppressor of cytokine signaling 3 regulates CD8 T-cell proliferation by inhibition of interleukins 6 and 27
- Brender, C; Tannahill, GM; Jenkins, BJ; Fletcher, J; Columbus, R; Saris, CJM; Ernst, M; Nicola, NA; Hilton, DJ; Alexander, WS; Starr, R;
Publication Year 2007-10-01, Volume 110, Issue #7, Page 2528-2536
- Journal Title
- Publication Type
- Journal Article
- Suppressor of cytokine signaling (SOCS) proteins regulate the intensity and duration of cytokine responses. SOCS3 is expressed in peripheral T cells, and recent reports have suggested that overexpression of SOCS3 modulates antigenand/or costimulation-induced T-cell activation. To study the role of SOCS3 in the regulation of T-cell activation, we used a conditional gene-targeting strategy to generate mice that lack SOCS3 in T/natural killer T cells (Socs3(Delta Lck/Delta Lck) mice). SOCS3-deficient CD8 T cells showed greater proliferation than wild-type cells in response to T-cell receptor (TCR) ligation despite normal activation of signaling pathways downstream from TCR or CD28 receptors. Signaling in response to the gp130 cytokines interieukin (IL)-6 and IL-27 was prolonged in SOCS3(Delta Lck/Delta Lck) T cells, and T cells from gp130(Y757F/Y757F) mice, in which the SOCS3-binding site on gp130 is ablated, showed a striking similarity to SOCS3-deficient CD8 T cells. Although the proliferative defect of Socs3(Delta Lck/Delta Lck) T cells was not rescued in the absence of IL-6, suppression of IL-27 signaling was found to substantially reduce anti-CD3-induced proliferation. We conclude that enhanced responses to TCR ligation by SOCS3-deficient CD8 T cells are not caused by aberrant TCR-signaling pathways but, rather, that increased IL-27 signaling drives unregulated proliferation in the absence of SOCS3.
- AMER SOC HEMATOLOGY
- MICE LACKING SUPPRESSOR; RECEPTOR SUBUNIT GP130; CYTOKINE SIGNALING-1; HELPER-CELLS; IL-2 PRODUCTION; IN-VIVO; TH1 DIFFERENTIATION; TCR STIMULATION; TRANSGENIC MICE; ACTIVATION
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Creation Date: 2007-10-01 12:00:00Last Modified: 0001-01-01 12:00:00