Regulatory T cells: recommendations to simplify the nomenclature

Abbas, Abul K.; Benoist, Christophe; Bluestone, Jeffrey A.; Campbell, Daniel; Ghosh, Sankar; Hori, Shohei; Jiang, Shuiping; Kuchroo, Vijay K.; Mathis, Diane; Roncarolo, Maria Grazia; Rudensky, Alexander Y.; Sakaguchi, Shimon; Shevach, Ethan M.; Vignali, Dario; Ziegler, Steve

doi:10.1038/ni.2554

Cited by 536 publications

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“…However, using PCR array analysis, we did not find a difference in IL-10 expression between WT and HO-1 Het NEC pups. It is also conceivable that HO-1 is able to increase the peripherally-derived Treg populations (often also referred to as inducible Tregs (iTregs)) (29). Our methodology used to identify FOXP3 + Tregs in the intestine did not enable us to distinguish between thymus-and peripherally derived Tregs.…”

Section: Correlation Of Treg/teff Ratios and Nec Scoresmentioning

confidence: 94%

Heme oxygenase-1 confers protection and alters T-cell populations in a mouse model of neonatal intestinal inflammation

et al. 2015

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Background: Necrotizing enterocolitis (NEC), an intestinal inflammatory disease affecting premature infants, is associated with low regulatory T (Treg) to effector T (Teff ) cell ratios. We recently demonstrated that heme oxygenase-1 (HO-1) deficiency leads to increased NEC development. Here, we investigated the effects of HO-1 on T-cell proportions in a murine NEC-like injury model. Methods: Intestinal injury was induced in 7-d-old wildtype (WT) or HO-1 heterozygous (HO-1 Het) pups by formulafeeding every 4 h for 24-78 h by oral gavage and exposures to 5%O 2 . Controls remained breastfed. HO-1 was induced in WT pups by administering heme preinjury induction. Lamina propria T cells were identified by flow cytometry. For adoptive transfer studies, WT splenic/thymic Tregs were injected intraperitoneally into HO-1 Het pups 12-24 h preinduction. results: Het mice showed increased intestinal injury and decreased Treg/Teff ratios. Genes for pattern recognition (Toll-like receptor-4, C-reactive protein, MyD88) and neutrophil recruitment increased in Het pups after NEC induction. Inducing intestinal HO-1 decreased NEC scores and incidence, and increased Treg/Teff ratios. Moreover, adoptive transfer of Tregs from WT to HO-1 Het pups decreased NEC scores and incidence and restored Treg/Teff ratios. conclusion: HO-1 can change Treg proportions in the lamina propria of young mice under inflammatory conditions, which might, in part, confer intestinal protection.n EC is a devastating disease of premature infants.Characterized by intestinal inflammation, it can progress rapidly to intestinal necrosis. Its incidence correlates inversely with low birth weight and gestational age, reaching ~7% in infants weighing 500-1,500 g. Unfortunately, 20-40% of NEC patients need to undergo surgery, which increases mortality up to 50% and places these infants at higher risk for developing long-term sequelae, such as short bowel syndrome and neurodevelopmental impairments (1).Although advances in the understanding of its pathophysiology have been made in the last decades, the pathogenesis of NEC remains incompletely understood. Thus, current prevention and treatment strategies are limited. Three factors are generally present when NEC occurs: (i) an immature intestinal barrier and immune system; (ii) enteral feedings; and (iii) a putative bacterial component. A genetic predisposition, an in utero maternal or fetal insult (hypoxia), and/or a highly immune-reactive intestinal mucosa may then cause the initial inflammation that precedes NEC (2).Several studies have demonstrated the importance of the innate immune system in the pathophysiology of NEC. For example, a significant component is the pattern recognition of pathogens through Toll-like receptor (TLR)-4 (3,4). Also, a reduction in Paneth and in mucin-producing goblet cells (5,6) and an increase in proinflammatory mediators (i.e., TNF-α, IL-1, -6, -8, and platelet-activating factor) are associated with NEC (7).However, less attention has been given to the adaptive immune system. The fact th...

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Section: Correlation Of Treg/teff Ratios and Nec Scoresmentioning

confidence: 94%

Heme oxygenase-1 confers protection and alters T-cell populations in a mouse model of neonatal intestinal inflammation

et al. 2015

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Section: Analyses Of the Regulatory T (Tregmentioning

confidence: 99%

“…In human and mice [2,3], Treg been described so far: natural Treg cells, which arise in the thymus [7], renamed tTreg cells [8], and induced Treg cells, which differentiate from naïve CD4…”

Section: Introductionmentioning

confidence: 99%

“…45: 1524Immunol. -1534 Molecular immunology 1525 been described so far: natural Treg cells, which arise in the thymus [7], renamed tTreg cells [8], and induced Treg cells, which differentiate from naïve CD4 + precursors in the periphery [9,10].Recently, the wide range of Treg-cell functional properties has been associated with phenotypical heterogeneity, such as their homing [6] and their activation status, that defines their anatomical location and homeostasis [11][12][13][14]. How Treg-cell antigen specificity relates to these functions remains poorly understood.…”

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confidence: 99%

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TCR sequences and tissue distribution discriminate the subsets of naïve and activated/memory Treg cells in mice

et al. 2015

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Analyses of the regulatory T (TregEur. J. Immunol. 2015Immunol. . 45: 1524Immunol. -1534 Molecular immunology 1525 been described so far: natural Treg cells, which arise in the thymus [7], renamed tTreg cells [8], and induced Treg cells, which differentiate from naïve CD4 + precursors in the periphery [9,10].Recently, the wide range of Treg-cell functional properties has been associated with phenotypical heterogeneity, such as their homing [6] and their activation status, that defines their anatomical location and homeostasis [11][12][13][14]. How Treg-cell antigen specificity relates to these functions remains poorly understood. Indeed, while Treg-cell activation is largely antigen-specific, the nature of their recognized antigens is still unclear. Theoretically, protecting normal tissues with Treg cells could be handled by a very restricted set of Treg cells specifically recognizing ubiquitously expressed self-antigens. However, many studies concluded that the Treg TCR repertoire is as complex as the effector T (Teff) cell repertoire [15][16][17][18], suggesting that the set of self-antigens recognized by Treg cells is quite complex and may be different at distinct anatomical location [11,19]. Deciphering the nature of the Treg-cell repertoire is of utmost importance for the understanding of their biology.Indeed, it is believed that during thymocyte differentiation, the affinity of the interaction between the TCRs and antigens presented onto thymic antigen-presenting cells (APCs) determines the fate of each cell [20]. The current paradigm is that of a mostly instructive process in which signaling from high-affinity TCRs, likely self-antigen specific, leads to negative selection except for a fraction of cells that will be selected to become Treg cells [21]. Hierarchical clustering of perturbation scores (Fig. 2B, top) discriminates Teff samples from nTreg-cell and amTreg-cell samples. Treg-cell subsets are dispersed into two clusters (I and II), while all but two Teff-cell samples are found in cluster III. Principal component analysis (PCA) projection (Fig. 2B, bottom) depicts this overlap between amTreg-cell and nTreg-cell repertoires.We then focused on amTreg-cell and nTreg-cell samples only and used their perturbation scores against Teff-cell samples to perform a hierarchical clustering according to their LNs localization. Hierarchical clustering leads to two clusters (I and II) (Fig. 2C, top) discriminating deep LNs samples in cluster I, while cluster II mainly gathers superficial LNs samples. Noteworthy, the first component of the PCA projection (PC1), which captures 43% of variability, mainly correlates with sample localization (Fig. 2C, bottom), indicating an increased gradation of perturbation from superficial LN nTreg cells to deep LN amTreg cells.Altogether, hierarchical clustering and PCA separated the different population repertoires, with amTreg cells repertoire being the more perturbed and more distant from that of Teff cells. Furthermore, the PCA projection also showed a rather high interindivi...

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“…Further investi-gations have led to the discovery of two unique subgroups of Tregs, their thymic Tregs (tTreg) (in older literature, referred to as natural T regulatory cell [nTreg]) and Tregs induced in the periphery (pTreg) (in older literature, referred to as inducible T regulatory cell [iTreg]). 17 Although tTreg formation is not yet fully understood, it is known that tTregs are differentiated within the thymus through a series of interactions with major histocompatibility complex (MHC) self peptides. 18 However, pTregs are converted peripherally from other CD4 ϩ T cells through expression of transforming growth factor beta (TGF) ␤ and the CNS1 gene.…”

Section: Treg Development and Functionmentioning

confidence: 99%