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

J Exp Med. 2006 Jan 23;203(1):165-75. doi: 10.1084/jem.20051836. Epub 2006 Jan 3.

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • CD4 Antigens
  • CD8 Antigens
  • Carrier Proteins / immunology
  • Carrier Proteins / metabolism
  • Cells, Cultured
  • Interleukin-4 / pharmacology
  • Interleukin-7 / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / metabolism*
  • Receptors, Interleukin-7 / immunology
  • Receptors, Interleukin-7 / metabolism*
  • Repressor Proteins / immunology
  • Repressor Proteins / metabolism
  • Signal Transduction
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins / immunology
  • Suppressor of Cytokine Signaling Proteins / metabolism
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*

Substances

  • CD4 Antigens
  • CD8 Antigens
  • Carrier Proteins
  • Il4ra protein, mouse
  • Interleukin-7
  • Receptors, Antigen, T-Cell
  • Receptors, Cell Surface
  • Receptors, Interleukin-7
  • Repressor Proteins
  • Socs1 protein, mouse
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • interleukin-7 receptor, alpha chain
  • Interleukin-4