Early TCR expression and aberrant T cell development in mice with endogenous prerearranged T cell receptor genes

J Immunol. 2007 Jul 15;179(2):928-38. doi: 10.4049/jimmunol.179.2.928.

Abstract

The factors that regulate the rate of production of T cells by the thymus remain incompletely defined. To test whether generation of functional T cell receptors limits the rate of thymic T cell export, we made use of a line of mice, LN3alphabeta, that have endogenously prerearranged TCR genes. The prerearranged TCR genes were expressed abnormally early in hemopoietic development, indicating that RAG-mediated recombination, rather than transcription factor expression, is the key determinant of the initiation of robust TCR transcription. Thymic T cell export rates were similar between wild-type (wt) and LN3alphabeta mice, indicating that T cell maturation rates in these mice are determined by factors other than TCR gene rearrangement. In competitive bone marrow chimeras, however, LN3alphabeta thymocytes were out-competed by wt cells and failed to develop beyond the double-negative 4 stage. Furthermore, wt progenitors transplanted intrathymically into LN3alphabeta mice proliferated excessively, suggesting that increased proliferative signals in the LN3alphabeta thymus compensate for faulty T cell development driven by early TCR expression.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / immunology
  • Flow Cytometry
  • Gene Rearrangement, T-Lymphocyte / genetics
  • Gene Rearrangement, T-Lymphocyte / immunology
  • Genes, RAG-1
  • Mice
  • Mice, Mutant Strains
  • Nuclear Transfer Techniques
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / growth & development*
  • Thymus Gland / immunology

Substances

  • Receptors, Antigen, T-Cell