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Non-obese diabetic mice select a low-diversity repertoire of natural regulatory T cells

Ferreira, Christina, Singh, Yogesh, Furmanski, Anna L., Wong, Florence Susan, Garden, Oliver A. and Dyson, Julian 2009. Non-obese diabetic mice select a low-diversity repertoire of natural regulatory T cells. Proceedings of the National Academy of Sciences of the United States of America 106 (20) , pp. 8320-8325. 10.1073/pnas.0808493106

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Abstract

Thymus-derived Foxp3+ natural regulatory CD4 T cells (nTregs) prevent autoimmunity through control of pathogenic, autoreactive T cells and other immune effector cells. Using T cell receptor (TCR) transgenic models, diversity within this lineage has been found to be similar to that of conventional CD4 T cells. To determine whether balanced TCR diversity may be perturbed in autoimmunity, we have analyzed receptor composition in C57BL/6 and autoimmune non-obese diabetic (NOD) mice. The natural regulatory and conventional CD4 repertoires of C57BL/6 had similar diversities. Despite the apparently normal thymic development of the NOD nTreg lineage, TCR diversity within the selected repertoire was markedly restricted. Detailed analysis of TCRα and -β chain composition is consistent with positive selection into the natural regulatory lineage being under stringent audition for interaction with MHC class II/self-peptide. The NOD MHC region, including the unique H2-Ag7 class II molecule, partly accounts for the reduction in diversity, but additional NOD genetic contribution(s) are required for complete repertoire compaction. Mechanistic links between MHC, autoimmunity, and nTreg diversity identified in this study are discussed.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > RZ Other systems of medicine
Uncontrolled Keywords: diabetes; NOD mice; TCR repertoire; thymic selection
Publisher: National Academy of Sciences
ISSN: 0027-8424
Last Modified: 04 Jun 2017 03:42
URI: http://orca.cf.ac.uk/id/eprint/25173

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