Rescued tolerant CD8 T cells are preprogrammed to reestablish the tolerant state

Science. 2012 Feb 10;335(6069):723-7. doi: 10.1126/science.1214277. Epub 2012 Jan 19.


Tolerant self-antigen-specific CD8 T cells fail to proliferate in response to antigen, thereby preventing autoimmune disease. By using an in vivo mouse model, we show that tolerant T cells proliferate and become functional under lymphopenic conditions, even in a tolerogenic environment. However, T cell rescue is only transient, with tolerance reimposed upon lymphorepletion even in the absence of tolerogen (self-antigen), challenging the prevailing paradigm that continuous antigen exposure is critical to maintain tolerance. Genome-wide messenger RNA and microRNA profiling revealed that tolerant T cells have a tolerance-specific gene profile that can be temporarily overridden under lymphopenic conditions but is inevitably reimposed, which suggests epigenetic regulation. These insights into the regulatory mechanisms that maintain or break self-tolerance may lead to new strategies for the treatment of cancer and autoimmunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Autoantigens / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / physiology
  • CD8-Positive T-Lymphocytes / transplantation
  • Cell Proliferation
  • Epigenesis, Genetic
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Homeostasis
  • Immunologic Memory
  • Lymphocyte Activation
  • Lymphocyte Count
  • Lymphopenia / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Self Tolerance* / genetics
  • Signal Transduction
  • T-Lymphocyte Subsets / immunology


  • Autoantigens
  • MicroRNAs
  • mirn181 microRNA, mouse

Associated data

  • GEO/GSE32025