The Journal of Experimental Medicine
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Published online 3 January 2006 doi:10.1084/jem.20051836
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 1, 165-175
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ARTICLE

 Cytokine signal transduction is suppressed in preselection double-positive thymocytes and restored by positive selection

Qing Yu1, Jung-Hyun Park1, Loretta L. Doan1, Batu Erman2, Lionel Feigenbaum3, and Alfred Singer1

1 Experimental Immunology Branch, National Cancer Institute (NCI), Bethesda, MD 20892
2 Faculty of Engineering and Natural Sciences, Sabanci University, 34956 Istanbul, Turkey
3 Science Applications International Corporation–Frederick, Inc., NCI-Frederick Cancer Research and Development Center, Frederick, MD 21702

CORRESPONDENCE Alfred Singer: singera{at}nih.gov

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.

Abbreviations used: DP, double positive; EMSA, electrophoretic mobility shift assay; {gamma}c, common gamma chain; LNT cell, lymph node T cell; p-Stat5, phospho-Stat5; SP, single positive; SOCS, suppressor of cytokine signaling; TFU, total fluorescence unit.

Q. Yu and J.-H. Park contributed equally to this work.

Q. Yu's present address is Laboratory of Immunology, National Institute on Aging, Baltimore, MD 21224.


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