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.
Pubmed ID: 22267581 RIS Download
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
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.