Homeostasis and function of regulatory T cells (Tregs) in vivo: Lessons from TCR-transgenic Tregs
Abstract
The identification of CD25 and subsequently Forkhead box protein 3 (Foxp3) as markers for regulatory T cells (Tregs) has revolutionized our ability to explore this population experimentally. In a similar vein, our understanding of antigen-specific Treg responses in vivo owes much to the fortuitous generation of T-cell receptor (TCR)-transgenic Tregs. This has permitted tracking of Tregs with a defined specificity in vivo, facilitating analysis of how encounter with cognate antigen shapes Treg homeostasis and function. Here, we review the key lessons learned from a decade of analysis of TCR-transgenic Tregs and set this in the broader context of general progress in the field. Use of TCR-transgenic Tregs has led to an appreciation that Tregs are a highly dynamic proliferative population in vivo, rather than an anergic population as they were initially portrayed. It is now clear that Treg homeostasis is positively regulated by encounter with self-antigen expressed on peripheral tissues, which is likely to be relevant to the phenomenon of peripheral repertoire reshaping that has been described for Tregs and the observation that the Treg TCR specificities vary by anatomical location. Substantial evidence has also accumulated to support the role of CD28 costimulation and interleukin-2 in Treg homeostasis. The availability of TCR-transgenic Tregs has enabled analysis of Treg populations that are sufficient or deficient in particular genes, without the comparison being confounded by repertoire alterations. This approach has yielded insights into genes required for Treg function in vivo, with particular progress being made on the role of ctla-4 in this context. As the prospect of manipulating Treg populations in the clinic becomes reality, a full appreciation of the rules governing their homeostasis will prove increasingly important. © 2014 The Authors. Immunological Reviews Published by John Wiley & Sons Ltd.Citation
Attridge, K. and Walker, L. S. K. (2014) Homeostasis and function of regulatory T cells (Tregs) in vivo: Lessons from TCR-transgenic Tregs, Immunological Reviews, 259 (2014), pp. 23-39.Publisher
WileyJournal
Immunological ReviewsPubMed ID
24712457Additional Links
https://onlinelibrary.wiley.com/doi/full/10.1111/imr.12165Type
Journal articleLanguage
enISSN
0105-2896EISSN
1600-065Xae974a485f413a2113503eed53cd6c53
10.1111/imr.12165
Scopus Count
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Except where otherwise noted, this item's license is described as Licence for published version: Creative Commons Attribution 4.0 International
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