| First Author | Brender C | Year | 2007 |
| Journal | Blood | Volume | 110 |
| Issue | 7 | Pages | 2528-36 |
| PubMed ID | 17609432 | Mgi Jnum | J:147013 |
| Mgi Id | MGI:3839084 | Doi | 10.1182/blood-2006-08-041541 |
| Citation | Brender C, et al. (2007) Suppressor of cytokine signaling 3 regulates CD8 T-cell proliferation by inhibition of interleukins 6 and 27. Blood 110(7):2528-36 |
| abstractText | 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 antigen- and/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(DeltaLck/DeltaLck) 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 interleukin (IL)-6 and IL-27 was prolonged in Socs3(DeltaLck/DeltaLck) 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(DeltaLck/DeltaLck) 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. |
