ArticleFrontiers in immunology2013
Do Natural T Regulatory Cells become Activated to Antigen Specific T Regulatory Cells in Transplantation and in Autoimmunity?
Article in Frontiers in immunology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
- CD56Haematologica · 2017Trial
- Cytokines Associated with Activation of CD4International journal of molecular sciences · 2026Review
- Transplant Tolerance, Not Only Clonal Deletion.Frontiers in immunology · 2022Review
- CD4Frontiers in immunology · 2022Review
- Multiple sclerosis patients have reduced resting and increased activated CD4Scientific reports · 2021Article
- Regulatory T Cell Plasticity and Stability and Autoimmune Diseases.Clinical reviews in allergy & immunology · 2020Review
- Fractalkine mediates lymphocyte inflammation and tubulointerstitial lesions by modifying the Treg/Th17 balance in lupus-prone MRL/lpr mice.American journal of translational research · 2020Article
- Plasma IL-5 but Not CXCL13 Correlates With Neutralization Breadth in HIV-Infected Children.Frontiers in immunology · 2019Article
- Immune activation and regulatory T cells in Mycobacterium tuberculosis infected lymph nodes.BMC immunology · 2018Article
- Interleukin-5 Mediates Parasite-Induced Protection against Experimental Autoimmune Encephalomyelitis: Association with Induction of Antigen-Specific CD4Frontiers in immunology · 2017Article
- Article
- T Cells: Soldiers and Spies--The Surveillance and Control of Effector T Cells by Regulatory T Cells.Clinical journal of the American Society of Nephrology : CJASN · 2015Review
- 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.BMC immunology · 2015Article
- Immunoendocrine dysbalance during uncontrolled T. cruzi infection is associated with the acquisition of a Th-1-like phenotype by Foxp3(+) T cells.Brain, behavior, and immunity · 2015Article
- The immunotherapeutic role of regulatory T cells in Leishmania (Viannia) panamensis infection.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Thymus-Derived, Peripherally Derived, and in vitro-Induced T Regulatory Cells.Frontiers in immunology · 2014Article
- Interleukin-12 (IL-12p70) Promotes Induction of Highly Potent Th1-Like CD4(+)CD25(+) T Regulatory Cells That Inhibit Allograft Rejection in Unmodified Recipients.Frontiers in immunology · 2014Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antigen specific T regulatory cells (Treg) are often CD4(+)CD25(+)FoxP3(+) T cells, with a phenotype similar to natural Treg (nTreg). It is assumed that nTreg cannot develop into an antigen specific Treg as repeated culture with IL-2 and a specific antigen does not increase the capacity or potency of nTreg to promote immune tolerance or suppress in vitro. This has led to an assumption that antigen specific Treg mainly develop from CD4(+)CD25(-)FoxP3(-) T cells, by activation with antigen and TGF-β in the absence of inflammatory cytokines such as IL-6 and IL-1β. Our studies on antigen specific CD4(+)CD25(+) T cells from animals with tolerance to an allograft, identified that the antigen specific and Treg are dividing, and need continuous stimulation with specific antigen T cell derived cytokines. We identified that a variety of cytokines, especially IL-5 and IFN-γ but not IL-2 or IL-4 promoted survival of antigen specific CD4(+)CD25(+)FoxP3(+) Treg. To examine if nTreg could be activated to antigen specific Treg, we activated nTreg in culture with either IL-2 or IL-4. Within 3 days, antigen specific Treg are activated and there is induction of new cytokine receptors on these cells. Specifically nTreg activated by IL-2 and antigen express the interferon-γ receptor (IFNGR) and IL-12p70 (IL-12Rβ2) receptor but not the IL-5 receptor (IL-5Rα). These cells were responsive to IFN-γ or IL-12p70. nTreg activated by IL-4 and alloantigen express IL-5Rα not IFNGR or IL-12p70Rβ2 and become responsive to IL-5. These early activated antigen specific Treg, were respectively named Ts1 and Ts2 cells, as they depend on Th1 or Th2 responses. Further culture of Ts1 cells with IL-12p70 induced Th1-like Treg, expressing IFN-γ, and T-bet as well as FoxP3. Our studies suggest that activation of nTreg with Th1 or Th2 responses induced separate lineages of antigen specific Treg, that are dependent on late Th1 and Th2 cytokines, not the early cytokines IL-2 and IL-4.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.