Cord Blood Derived CD4+CD25high T Cells Become Functional Regulatory T Cells upon Antigen Encounter

Mayer, Eric; Bannert, Christina; Gruber, Saskia; Klunker, Sven; Spittler, Andreas; Akdiş, Cezmi A.; Szépfalusi, Zsolt; Eiwegger, Thomas

doi:10.1371/journal.pone.0029355

Cited by 39 publications

(36 citation statements)

References 46 publications

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“…To avoid differences in the Treg suppression capabilities between adults and newborns as a consequence of their naïve phenotype, we pre-activated Treg before adding Tcon and measured suppressive activity. Pre-acti-vated term Treg were fully suppressive, similar to previous data [41,47–49]. However, in contrast to the data reported by Fan et al, we did not find Treg from term CB to be more suppressive than adult Treg [48].…”

Section: Discussionsupporting

confidence: 88%

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Effect of chorioamnionitis on regulatory T cells in moderate/late preterm neonates

et al. 2015

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Regulatory T-cells (Treg) have a protective role for the control of immune activation and tissue damage. The effects of chorioamnionitis (chorio) on Treg in moderate/late preterm newborns are not known. We hypothesized that infants exposed to chorio would have decreased Treg frequency and/or function. We isolated mononuclear cells from adult peripheral blood and cord blood from term and moderate/late preterm infants who were classified for severity of chorio exposure. Mononuclear cells were analyzed by flow cytometry for Treg frequency and phenotype. Treg suppression of activation of conventional T-cells (Tcon) was also quantified. Treg frequencies were similar in all groups of neonates, but lower than that found in adults. Newborn Treg had a naïve phenotype, with decreased levels of CD45RO, HLA-DR, CD39 and TIGIT compared to adult Treg and chorio did not affect the phenotype. Treg from preterm newborns exposed to severe chorio had higher expression of Ki67 compared to the other groups. Treg from preterm newborns were less suppressive than Treg from adults or term, and the level of suppression was reduced with severe chorio. Relative to term, Treg frequency and phenotype were not affected by prematurity and chorio but their functionality was decreased. Lower Treg activity may contribute to inflammation in newborns that is often associated with chorioamnionitis.

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Section: Discussionsupporting

confidence: 88%

“…However, compared to adults these cells are less potent due to their phenotypic immaturity [47]. To avoid differences in the Treg suppression capabilities between adults and newborns as a consequence of their naïve phenotype, we pre-activated Treg before adding Tcon and measured suppressive activity.…”

Section: Discussionmentioning

confidence: 99%

Effect of chorioamnionitis on regulatory T cells in moderate/late preterm neonates

et al. 2015

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“…Treg subsets including natural Treg (nTreg, derived from the thymus) and induced Treg (iTreg, derived from the periphery from Teff cells) have been described 28–31 . iTreg can be characterized as CD4+CD25 hi cells that proliferate in response to specific antigens (i.e., CFSE lo or CD40L/CD69+) 32–35 . iTreg can be Foxp3+ and/or TGF-β+ and/or IL-10+ 32,34,36,37,49,68 .…”

Section: Introductionmentioning

confidence: 99%

“…iTreg can be characterized as CD4+CD25 hi cells that proliferate in response to specific antigens (i.e., CFSE lo or CD40L/CD69+) 32–35 . iTreg can be Foxp3+ and/or TGF-β+ and/or IL-10+ 32,34,36,37,49,68 . Type 1 regulatory T cells (Tr1) release IL-10 28,38,39 and express CD4, CD49, and LAG3 on their surface 28,38,39 which differs from nTreg expressing CD4, CD25 hi , CD127 lo , and perhaps by Helios on their surface 25–27,40–43 .…”

Section: Introductionmentioning

confidence: 99%

Peanut oral immunotherapy results in increased antigen-induced regulatory T-cell function and hypomethylation of forkhead box protein 3 (FOXP3)

Syed

Garcia

Lyu

et al. 2014

Journal of Allergy and Clinical Immunology

422

412

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Background The mechanisms contributing to clinical immune tolerance remain incompletely understood. This study provides evidence for specific immune mechanisms that are associated with a model of operationally defined clinical tolerance. Objective Our overall objective was to study laboratory changes associated with clinical immune tolerance in antigen-induced T cells, basophils, and antibodies in subjects undergoing oral immunotherapy (OIT) for peanut allergy. Methods In a phase 1, single site study, we studied participants (n=23) undergoing peanut OIT and compared them to age-matched allergic controls (n=20) undergoing standard of care (abstaining from peanut) for 24 months. Participants were operationally defined as clinically immune tolerant (IT) if they had no detectable allergic reactions to a peanut oral food challenge after 3 months of therapy withdrawal (IT, n=7) while those that had an allergic reaction were categorized as non-tolerant (NT, n=13). Results Antibody and basophil activation measurements did not statistically differentiate between NT vs. IT. However, T-cell function and demethylation of FOXP3 CpG sites in antigen-induced Treg were significantly different between IT vs. NT participants. When IT participants were withdrawn from peanut therapy for an additional 3 months (total of 6 months); only 3 participants remained "immune tolerant" and 4 participants regained sensitivity along with increased methylation of FOXP3 CpG sites in antigen-induced Treg. Conclusion In summary, modifications at the DNA level of antigen-induced T-cell subsets may be predictive of a state of operationally-defined clinical "immune tolerance" during peanut OIT.

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“…In contrast to adult PB, the majority of CB Tregs expresses naïve markers and does not initially show suppressor activity [166,167]. However, upon antigenic stimulation, these cells upregulate CD25, CTLA-4, and FOXP3, proliferating with a higher expansion capacity compared to adult Tregs and posses potent suppressive activity [166,167].…”

Section: Regulatory T Cellsmentioning

confidence: 99%

Current Strategies to Improve Engraftment in Cord Blood Transplantation

Danby

Rocha²

2014

J Stem Cell Res Ther

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Umbilical cord blood (UCB) remains an important alternative source of hematopoietic stem cells (HSC) for allogeneic transplantation when suitable HLA-matched donors are unavailable. Cord blood (CB) offers many benefits including rapid availability, absence of risk to the donor, and a low incidence of graft-versus-host disease. However, although the overall survival of patients receiving unrelated CB transplants is comparable to using other HSC sources, UCB transplantation is associated with delayed engraftment and poor immune reconstitution, particularly in adults. While this is partly due to the lower cell dose in UCB grafts, it may also reflect the relative immaturity of cord blood. Therefore, many different strategies to enhance hematopoietic engraftment following UCB transplantation are currently under investigation. This article will review the latest techniques including improved collection, HLAmatching, homing and expansion of CB, and the use of double CB grafts, third-party donors, and accessory cells. As many of these methods are now in clinical trials, it is anticipated that UCB transplantation will continue to improve, further expanding our understanding of CB biology and HSC transplantation.

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Cord Blood Derived CD4+CD25high T Cells Become Functional Regulatory T Cells upon Antigen Encounter

Cited by 39 publications

References 46 publications

Effect of chorioamnionitis on regulatory T cells in moderate/late preterm neonates

Effect of chorioamnionitis on regulatory T cells in moderate/late preterm neonates

Peanut oral immunotherapy results in increased antigen-induced regulatory T-cell function and hypomethylation of forkhead box protein 3 (FOXP3)

Current Strategies to Improve Engraftment in Cord Blood Transplantation

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