Self-reactivity in thymic double-positive cells commits cells to a CD8 alpha alpha lineage with characteristics of innate immune cells

Nat Immunol. 2004 Jun;5(6):597-605. doi: 10.1038/ni1070. Epub 2004 May 9.


Thymocytes displaying self-reactive T cell receptors usually undergo negative selection in the thymus. Here we demonstrate that agonist peptides can promote positive selection of immature double-positive thymocytes into distinct lineages, varying with the agonist concentration and the animal's age. Microarray gene expression analyses showed broad transcriptional alterations in a set of transcripts associated with the innate immune system, as well as silencing of CD8 beta expression. The resulting CD8 alpha alpha T cells showed a rapid effector cytokine response. Hence, T cells displaying self-reactive receptors can have the gene expression profile and phenotypic characteristics of innate immune cells.

Publication types

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

MeSH terms

  • Animals
  • Autoimmunity / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / physiology
  • Cell Differentiation / immunology
  • Cell Differentiation / physiology*
  • Dose-Response Relationship, Drug
  • Gene Expression / physiology
  • Gene Expression Profiling
  • Immunity, Innate / immunology
  • Ligands
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Antigen, T-Cell / agonists
  • Thymus Gland / immunology*


  • Ligands
  • Receptors, Antigen, T-Cell