Positive selection by the pre-TCR yields mature CD8+ T cells

J Immunol. 2002 Nov 1;169(9):4913-9. doi: 10.4049/jimmunol.169.9.4913.


It has been of much interest whether there is functional redundancy between the constitutively signaling pre-Talpha/TCRbeta (pre-TCR) and ligated TCRalphabeta complexes, which independently operate the two distinct checkpoints during thymocyte development, i.e., the pre-TCR involved in beta-selection at the CD4(-)CD8(-) double-negative stage and the TCRalphabeta being crucial for positive/negative selection at the CD4(+)CD8(+) double-positive stage. We found that the pre-TCR expressed on double-positive cells in TCRalpha-deficient (TCRalpha(-/-)) mice produced a small number of mature CD8(+) T cells. Surprisingly, when pre-Talpha was overexpressed, resulting in augmentation of pre-TCR expression, there was a striking increase of the CD8(+) T cells. In addition, even in the absence of up-regulation of pre-TCR expression, a similar increase of CD8(+) T cells was also observed in TCRalpha(-/-) mice overexpressing Egr-1, which lowers the threshold of signal strength required for positive selection. In sharp contrast, the CD8(+) T cells drastically decreased in the absence of pre-Talpha on a TCRalpha(-/-) background. Thus, the pre-TCR appears to functionally promote positive selection of CD8(+) T cells. The biased production of CD8(+) T cells via the pre-TCR might also support the potential involvement of signal strength in CD4/CD8 lineage commitment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / physiology
  • Animals
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • DNA-Binding Proteins / physiology
  • Early Growth Response Protein 1
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / physiology
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / physiology
  • Immediate-Early Proteins*
  • Interleukin-2 / biosynthesis
  • Lymphocyte Activation / genetics
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell, alpha-beta
  • Transcription Factors / physiology


  • Adjuvants, Immunologic
  • DNA-Binding Proteins
  • Early Growth Response Protein 1
  • Egr1 protein, mouse
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Immediate-Early Proteins
  • Interleukin-2
  • Membrane Glycoproteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Transcription Factors
  • pre-T cell receptor alpha