Publication Date:
2012-01-24
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3754789/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3754789/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schietinger, Andrea -- Delrow, Jeffrey J -- Basom, Ryan S -- Blattman, Joseph N -- Greenberg, Philip D -- K01 CA117985/CA/NCI NIH HHS/ -- P30 CA015704/CA/NCI NIH HHS/ -- P30 CA015704-35/CA/NCI NIH HHS/ -- P30 DK 56465/DK/NIDDK NIH HHS/ -- P30 DK056465/DK/NIDDK NIH HHS/ -- R01 CA033084/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2012 Feb 10;335(6069):723-7. doi: 10.1126/science.1214277. Epub 2012 Jan 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, University of Washington (UW), Seattle, WA 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22267581" target="_blank"〉PubMed〈/a〉
Keywords:
Adoptive Transfer
;
Animals
;
Autoantigens/immunology
;
CD8-Positive T-Lymphocytes/*immunology/physiology/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/metabolism
;
Oligonucleotide Array Sequence Analysis
;
*Self Tolerance/genetics
;
Signal Transduction
;
T-Lymphocyte Subsets/immunology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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