T cell receptor-mediated negative selection of autoreactive T lymphocyte precursors occurs after commitment to the CD4 or CD8 lineages

J Exp Med. 1990 Sep 1;172(3):835-45. doi: 10.1084/jem.172.3.835.

Abstract

To identify the maturational stage(s) during which T cell receptor (TCR)-mediated positive and negative selection occurs, we followed the development of CD4+8- and CD4-8+ T cells from TCRlo CD4+8+ thymic blasts in the presence of different positive and negative selecting (major histocompatibility complex or Mls) elements. We describe novel lineage-committed transitional intermediates that are TCRmed CD4+8lo or TCRmed CD4lo8+, and that show evidence of having been positively selected. Furthermore, negative selection is not evident until after cells have attained one of the TCRmed transitional phenotypes. Accordingly, we propose that negative selection in normal mice occurs only after TCRlo CD4+8+ precursors have been positively selected into either the CD4 or CD8 lineage.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • Antigens, Differentiation, T-Lymphocyte / isolation & purification
  • CD3 Complex
  • CD4 Antigens / immunology*
  • CD8 Antigens
  • Crosses, Genetic
  • Mice
  • Mice, Inbred Strains
  • Models, Biological
  • Oligonucleotide Probes
  • Polymerase Chain Reaction
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / isolation & purification
  • Species Specificity
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Thymus Gland / immunology*
  • Transcription, Genetic

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • CD4 Antigens
  • CD8 Antigens
  • Oligonucleotide Probes
  • Receptors, Antigen, T-Cell