CD4+CD25+Foxp3+IFN-γ+ human induced T regulatory cells are induced by interferon-γ and suppress alloresponses nonspecifically

Daniel, Volker; Sadeghi, Mahmoud; Wang, Haihao; Opelz, Gerhard

doi:10.1016/j.humimm.2011.05.020

Cited by 30 publications

(43 citation statements)

References 26 publications

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“…They are considered Th1-like Tregs, because they express T-bet and IFN-g. Of note, the continued presence of IL-2 blocks generation of Th1-like Tregs, suggesting that the current methods of Treg expansion with repeated IL-2 exposure may select against growth of antigen-specific activated Tregs (58). Th1-like Tregs occur in humans, including recipients of renal transplants (104).…”

Section: Il-2 Promotes Antigen-specific Tregsmentioning

confidence: 99%

T Cells

Hall

2015

Clinical Journal of the American Society of Nephrology

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Traditionally, T cells were CD4 1 helper or CD8 1 cytotoxic T cells, and with antibodies, they were the soldiers of immunity. Now, many functionally distinct subsets of activated CD4 1 and CD8 1 T cells have been described, each with distinct cytokine and transcription factor expression. For CD4 1 T cells, these include Th1 cells expressing the transcription factor T-bet and cytokines IL-2, IFN-g, and TNF-b; Th2 cells expressing GATA-3 and the cytokines IL-4, IL-5, and IL-13; and Th17 cells expressing RORgt and cytokines IL-17A, IL-17F, IL-21, and IL-22. The cytokines produced determine the immune inflammation that they mediate. T cells of the effector lineage can be naïve T cells, recently activated T cells, or memory T cells that can be distinguished by cell surface markers. T regulatory cells or spies were characterized as CD8 1 T cells expressing I-J in the 1970s. In the 1980s, suppressor cells fell into disrepute when the gene for I-J was not present in the mouse MHC I region. At that time, a CD4 1 T cell expressing CD25, the IL-2 receptor-a, was identified to transfer transplant tolerance. This was the same phenotype of activated CD4 1 CD25 1 T cells that mediated rejection. Thus, the cells that could induce tolerance and undermine rejection had similar badges and uniforms as the cells effecting rejection. Later, FOXP3, a transcription factor that confers suppressor function, was described and distinguishes T regulatory cells from effector T cells. Many subtypes of T regulatory cells can be characterized by different expressions of cytokines and receptors for cytokines or chemokines. In intense immune inflammation, T regulatory cells express cytokines characteristic of effector cells; for example, Th1-like T regulatory cells express T-bet, and IFN-g-like Th1 cells and effector T cells can change sides by converting to T regulatory cells. Effector T cells and T regulatory cells use similar molecules to be activated and mediate their function, and thus, it can be very difficult to distinguish soldiers from spies.

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Section: Il-2 Promotes Antigen-specific Tregsmentioning

confidence: 99%

T Cells

Hall

2015

Clinical Journal of the American Society of Nephrology

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“…In human renal transplant recipients with good long-term graft function, we observed an increased frequency of CD3 + CD4 + CD25 + Foxp3 + IFNγ + Treg in the circulation [12]. Human separated CD3 + CD4 + CD25 + Foxp3 + Treg that expressed IFNγ suppressed mixed lymphocyte cultures (MLC) antigen-unspecifically but showed the strongest suppression in antigen-specific settings [4,13,14]. Separated CD4 + CD25 + IFNγ + co-expressed Foxp3, IL4, IL10, and TGFß intracellularly, suggesting that the release of these immunosuppressive cytokines is involved in the immunosuppressive mechanism of IFNγ + iTreg [13].…”

Section: Introductionmentioning

confidence: 96%

“…Human separated CD3 + CD4 + CD25 + Foxp3 + Treg that expressed IFNγ suppressed mixed lymphocyte cultures (MLC) antigen-unspecifically but showed the strongest suppression in antigen-specific settings [4,13,14]. Separated CD4 + CD25 + IFNγ + co-expressed Foxp3, IL4, IL10, and TGFß intracellularly, suggesting that the release of these immunosuppressive cytokines is involved in the immunosuppressive mechanism of IFNγ + iTreg [13]. In patients with type 1 diabetes and untreated patients with relapsing remitting multiple sclerosis, the frequency of Foxp3 + IFNγ + Treg was significantly increased compared to healthy controls [15,16].…”

Section: Introductionmentioning

confidence: 99%

CD4+CD25+Foxp3+IFNγ+ Treg are immunosuppressive in vitro and increase with intensity of the alloresponse in pretransplant MLC

Daniel

Sadeghi

Wang

et al. 2012

Transplant Immunology

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“…Relevant to Treg activation and function, IFN-γ induces Th1-like Treg from tTreg that have been initially activated by IL-2 [53,[116][117][118][119]. IFN-γ acts on activated Treg to induce STAT1, which in turn induces t-bet and IFN-γ expression [120,121].…”

Section: Role Of Ifn-γ In Induction Of Antigen Specific Tregmentioning

confidence: 99%

“…Some studies have identified that these Th1-like Treg are antigen specific [91,122,123,130], while others report that their suppression is nonantigen specific [116,131]. Th1-like Treg express CXCR3 that promote migration to sites of Th1 mediated inflammation, and suppress Th1 responses in peripheral tissues [53,90].…”

Section: Role Of Ifn-γ In Induction Of Antigen Specific Tregmentioning

confidence: 99%