Regulatory T cells generated early in life play a distinct role in maintaining self-tolerance

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Title
Regulatory T cells generated early in life play a distinct role in maintaining self-tolerance
Author(s)
Siyoung Yang; N Fujikado; D Kolodin; C Benoist; D Mathis
Bibliographic Citation
Science, vol. 348, no. 6234, pp. 589-594
Publication Year
2015
Abstract
Aire is an important regulator of immunological tolerance, operating in a minute subset of thymic stromal cells to induce transcripts encoding peptides that guide T cell selection. Expression of Aire during a perinatal age window is necessary and sufficient to prevent the multiorgan autoimmunity characteristic of Aire-deficient mice. We report that Aire promotes the perinatal generation of a distinct compartment of Foxp3+CD4+ regulatory T (Treg) cells, which stably persists in adult mice. This population has a role in maintaining self-tolerance, a transcriptome and an activation profile distinguishable from those of Tregs produced in adults. Underlying the distinct Treg populations are age-dependent, Aire-independent differences in the processing and presentation of thymic stromal-cell peptides, resulting in different Tcell receptor repertoires. Our findings expand the notion of a developmentally layered immune system.
ISSN
0036-8075
Publisher
Amer Assoc Advancement Science
DOI
http://dx.doi.org/10.1126/science.aaa7017
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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