First Author | Yu Q | Year | 2006 |
Journal | J Exp Med | Volume | 203 |
Issue | 1 | Pages | 165-75 |
PubMed ID | 16390939 | Mgi Jnum | J:118814 |
Mgi Id | MGI:3700428 | Doi | 10.1084/jem.20051836 |
Citation | Yu Q, et al. (2006) Cytokine signal transduction is suppressed in preselection double-positive thymocytes and restored by positive selection. J Exp Med 203(1):165-75 |
abstractText | Death by neglect requires that CD4+8+ double-positive (DP) thymocytes avoid cytokine-mediated survival signals, which is presumably why DP thymocytes normally extinguish IL-7R gene expression. We report that DP thymocytes before positive selection (preselection DP thymocytes) fail to transduce IL-7 signals even when they express high levels of transgenic IL-7R on their surface, because IL-7R signal transduction is actively suppressed in preselection DP thymocytes by suppressor of cytokine signaling (SOCS)-1. SOCS-1 is highly expressed in preselection DP thymocytes, but it is down-regulated by T cell receptor-mediated positive selection signals. Interestingly, we found that the uniquely small cell volume of DP thymocytes is largely the result of absent IL-7 signaling in preselection DP thymocytes. We also report that, contrary to current concepts, preselection DP thymocytes express high levels of endogenously encoded IL-4Rs. However, their ability to transduce cytokine signals is similarly suppressed by SOCS-1. Thus, despite high surface expression of transgenic or endogenous cytokine receptors, cytokine signal transduction is actively suppressed in preselection DP thymocytes until it is restored by positive selection. |