PD‐1 regulates extrathymic regulatory T‐cell differentiation. Issue 9 (18th August 2014)

• Record Type: Journal Article
• Authors: Chen, Xiufen; Fosco, Dominick; Kline, Douglas E.; Meng, Liping; Nishi, Saki; Savage, Peter A.; Kline, Justin
• Is Part Of: European journal of immunology. Volume 44:Issue 9(2014:Sep.)
• Page Start: 2603
• Page End: 2616
• Publication Date: 2014-08-18
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201344423
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Treg cells and the programed death‐1/programed death ligand‐1 (PD‐1/PD‐L1) pathway are both critical for maintaining peripheral tolerance to self‐Ags. A significant subset of Treg cells constitutively expresses PD‐1, which prompted an investigation into the role of PD‐1/PD‐L1 interactions in Treg‐cell development, function, and induction in vivo. The phenotype and abundance of Treg cells was not significantly altered in PD‐1‐deficient mice. The thymic development of polyclonal and monospecific Treg cells was not negatively impacted by PD‐1 deficiency. The suppressive function of PD‐1^−/− Treg cells was similar to their PD‐1^+/+ counterparts both in vitro and in vivo. However, in three different in vivo experimental settings, PD‐1^−/− conventional CD4⁺ T cells demonstrated a strikingly diminished tendency toward differentiation into peripherally induced Treg (pTreg) cells. Our results demonstrate that PD‐1 is dispensable for thymic Treg‐cell development and suppressive function, but is critical for the extrathymic differentiation of pTreg cells in vivo. These data suggest that Ab blockade of the PD‐1/PD‐L1 pathway may augment T‐cell responses by acting directly on conventional T cells, and also by suppressing the differentiation of pTreg cells.</p> </abstract>