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

Andrea Schietinger, Jeffrey J. Delrow, Ryan S. Basom, Joseph Blattman, Philip D. Greenberg

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)723-727
Number of pages5
JournalScience
Volume335
Issue number6069
DOIs
StatePublished - Feb 10 2012

ASJC Scopus subject areas

  • General

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