Rescued Tolerant CD8 T Cells Are Preprogrammed to Reestablish the Tolerant State.
Schietinger, Andrea 1,2; Delrow, Jeffrey J. 3; Basom, Ryan S. 3; Blattman, Joseph N. 1,2,*; Greenberg, Philip D. 1,2,+
[Report]
Science.
335(6069):723-727, February 10, 2012.
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: 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.
Copyright (C) 2012 by the American Association for the Advancement of Science