Differential regulation of translation and eIF4E phosphorylation during human thymocyte maturation

J Immunol. 1998 Apr 1;160(7):3269-73.


Activation of peripheral blood T cells by cross-linking of CD3 results in a rapid and substantial rise in translation rates and proliferation, which coincides with an increase in the cap-binding protein, eIF4E activity. In contrast, immature CD4+ CD8+ double-positive (DP) thymocytes undergo apoptosis in response to anti-CD3 mAb. We have investigated translation initiation in the response of immature thymocytes to activating signals. Activation by anti-CD3 + anti-CD4 of immature CD4+ CD8+ DP thymocytes results in a rapid decrease in protein synthesis. In contrast, similar treatment of CD4+ or CD8+ single-positive (SP) thymocytes results in an increase in protein synthesis. The rate of protein synthesis is linked to the phosphorylation status of eIF4E. Following anti-CD3 + anti-CD4 stimulation, eIF4E phosphorylation strongly decreases in immature DP thymocytes, whereas it increases in mature SP thymocytes. The expression of 4E-BP2, a specific repressor of eIF4E function, is high in DP cells but decreases during maturation, raising the possibility of a role for 4E-BP2 in repressing eIF4E phosphorylation. These data provide evidence for differential regulation of the translational machinery during T cell development.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins / biosynthesis
  • Cell Cycle Proteins
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Child, Preschool
  • Cross-Linking Reagents
  • Eukaryotic Initiation Factor-4E
  • Eukaryotic Initiation Factors*
  • Humans
  • Immunophenotyping
  • Interphase / immunology
  • Lymphocyte Activation
  • Peptide Initiation Factors / genetics
  • Peptide Initiation Factors / metabolism*
  • Phosphoproteins / biosynthesis
  • Phosphorylation
  • Protein Biosynthesis*
  • Receptor-CD3 Complex, Antigen, T-Cell / metabolism
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Cell Cycle Proteins
  • Cross-Linking Reagents
  • EIF4EBP1 protein, human
  • EIF4EBP2 protein, human
  • Eukaryotic Initiation Factor-4E
  • Eukaryotic Initiation Factors
  • Peptide Initiation Factors
  • Phosphoproteins
  • Receptor-CD3 Complex, Antigen, T-Cell