Rescued tolerant CD8 T cells are preprogrammed to reestablish the tolerant state.
Science, 2012/2/10;335(6069):723-7.
Schietinger A[1], Delrow JJ, Basom RS, Blattman JN, Greenberg PD
Affiliations
PMID: 22267581DOI: 10.1126/science.1214277
Impact factor: 63.714
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.
MeSH terms
Adoptive Transfer; Animals; Autoantigens; CD8-Positive T-Lymphocytes; Cell Proliferation; Epigenesis, Genetic; Gene Expression Profiling; Gene Expression Regulation; Homeostasis; Immunologic Memory; Lymphocyte Activation; Lymphocyte Count; Lymphopenia; Mice; Mice, Inbred C57BL; Mice, Transgenic; MicroRNAs; Oligonucleotide Array Sequence Analysis; Self Tolerance; Signal Transduction; T-Lymphocyte Subsets
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