title: PD-1 regulates extrathymic regulatory T-cell differentiation.
abstract: 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.
authors: Department of Medicine, University of Chicago Comprehensive Cancer Center, Chicago, IL, USA.
authors: Xiufen
authors: X
authors: Chen
authors: Dominick
authors: D
authors: Fosco
authors: Douglas E
authors: DE
authors: Kline
authors: Liping
authors: L
authors: Meng
authors: Saki
authors: S
authors: Nishi
authors: Peter A
authors: PA
authors: Savage
authors: Justin
authors: J
authors: Kline
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D007108:Immune Tolerance / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
chemical_list: C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor
keywords: PD-1; Treg cell; Treg-cell development; Treg-cell differentiation; Treg-cell function