Cytokine signal transduction is suppressed in preselection double-positive thymocytes and restored by positive selection.
J Exp Med
; 203(1): 165-75, 2006 Jan 23.
Article
em En
| MEDLINE
| ID: mdl-16390939
ABSTRACT
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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1
Base de dados:
MEDLINE
Assunto principal:
Subpopulações de Linfócitos T
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Receptores de Superfície Celular
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Receptores de Interleucina-7
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article