ArticleBMC immunology2015
IFNγ+ Treg in-vivo and in-vitro represent both activated nTreg and peripherally induced aTreg and remain phenotypically stable in-vitro after removal of the stimulus.
Article in BMC immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- SATB1 is a targetable modulator of JAK-STAT signaling and cytokines in human Treg and Tconv cells.EMBO reports · 2026Article
- Treg-derived IFN-γ supports the differentiation of Th1-Treg in tumor immunity and autoimmunity.Frontiers in immunology · 2026Article
- IL-6 amplifies corneal transplant alloimmunity by inducing dysfunctional IFN-γ- secreting Treg through the VEGFA-VEGFR1 axis.Transplant immunology · 2025Article
- Discrepancy in the suppressive function of regulatory T cells in allergic asthmatic vs. allergic rhinitis subjects upon low-dose allergen challenges.Frontiers in allergy · 2023Article
- PD-L1 signaling selectively regulates T cell lymphatic transendothelial migration.Nature communications · 2022Article
- Circulating NKG2A-NKG2D+ CD56dimCD16+ Natural Killer (NK) Cells as Mediators of Functional Immunosurveillance in Kidney Transplant Recipients.Annals of transplantation · 2020Article
- Regulatory T cells control the dynamic and site-specific polarization of total CD4 T cells following Salmonella infection.Mucosal immunology · 2020Article
- Dynamic changes in the regulatory T-cell heterogeneity and function by murine IL-2 mutein.Life science alliance · 2020Article
- Regulatory T Cell Plasticity and Stability and Autoimmune Diseases.Clinical reviews in allergy & immunology · 2020Review
- Expanding Diversity and Common Goal of Regulatory T and B Cells. I: Origin, Phenotype, Mechanisms.Archivum immunologiae et therapiae experimentalis · 2017Review
- Association of peripheral NK cell counts with HeliosClinical and experimental immunology · 2017Article
- Changes in ReactivityFrontiers in immunology · 2017Article
- Article
- Low-dose oral cholecalciferol is associated with higher numbers of Helios(+) and total Tregs than oral calcitriol in renal allograft recipients: an observational study.BMC pharmacology & toxicology · 2016Observational
- Allostimulatory Effects of Dendritic Cells with Characteristic Features of a Regulatory Phenotype.PloS one · 2016Article
- Suppression of CD4+ Effector Responses by Naturally Occurring CD4+ CD25+ Foxp3+ Regulatory T Cells Contributes to Experimental Cerebral Malaria.Infection and immunity · 2016Article
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIFNγ-producing CD4+CD25+Foxp3+CD127- Treg represent the first line of Treg during an immune response. In the present study we determined whether IFNγ+ Treg in-vivo and in-vitro are Helios-positive representing activated natural (nTreg) or Helios-negative representing adaptive Treg (aTreg) and whether they originate from CD4+CD25+ and/or CD4+CD25- PBL. Furtheron, we investigated whether they are inducible by recombinant IFNγ (rIFNγ) as a single stimulus, decrease in-vitro after elimination of the stimulus, and have a demethylated Foxp3 Treg-specific demethylated region (TSDR) which is associated with stable Foxp3 expression.
methodSubsets of IFNγ+ Treg were determined in peripheral blood of healthy controls using eight-color flow cytometry and were further investigated in-vitro. Foxp3 TSDR methylation status was determined using bisulphite polymerase chain reaction (PCR) and high resolution melt (HRM) analysis.
resultsNearly all Treg in the peripheral blood were Helios+IFNγ- (1.9 ± 1.1/μl) and only few were Helios+IFNγ+ or Helios-IFNγ+ Treg (both 0.1 ± 0.1/μl). Enriched IFNγ+ Treg subsets showed in part strong Foxp3 TSDR demethylation. In-vitro, rIFNγ was unable to induce Treg. CD4+CD25+ enriched PBL stimulated with PMA/Ionomycin in the presence of rIFNγ were rather resistant to the effect of rIFNγ, in contrast to CD4+CD25- enriched PBL which showed increasing total Treg with Helios+ Treg switching from IFNγ- to IFNγ+ and increasing Helios-IFNγ+ Treg. The data indicate that rIFNγ, in combination with a polyclonal stimulus, activates nTreg and induces aTreg. When phorbol 12-myristate 13-acetate (PMA)/Ionomycin was washed out from the cell culture after 6 h stimulation, Treg induction continued for at least 96 h of cell culture, contradicting the hypothesis that removal of the stimulus results in significant decrease of IFNγ- and IFNγ+ CD4+CD25+Foxp3+CD127- Treg due to loss of Foxp3 expression.
conclusionsIFNγ+Helios- aTreg as well as IFNγ+Helios+ nTreg are detectable in the blood of healthy individuals, show in part strong Foxp3 TSDR demethylation and are inducible in-vitro. The present data provide further insight concerning the in-vivo and in-vitro characteristics of IFNγ+ Treg and help to understand their role in immunoregulation. Alloantigen-specific demethylated IFNγ+Helios+ nTreg might represent a suitable marker for monitoring graft-specific immunosuppression in renal transplant recipients.
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