Cytokine signal transduction is suppressed in preselection double-positive thymocytes and restored by positive selection
Yu, Qing and Park, Jung-Hyun and Doan, Loretta L. and Erman, Batu and Feigenbaum, Lionel and Singer, Alfred (2006) Cytokine signal transduction is suppressed in preselection double-positive thymocytes and restored by positive selection. Journal of experimental medicine, 203 (1). pp. 165-175. ISSN 0022-1007
Official URL: http://dx.doi.org/10.1084/jem.20051836
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.
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