2001
DOI: 10.1084/jem.194.5.629
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Cell Contact–Dependent Immunosuppression by Cd4+Cd25+Regulatory T Cells Is Mediated by Cell Surface–Bound Transforming Growth Factor β

Abstract: CD4+CD25+ T cells have been identified as a population of immunoregulatory T cells, which mediate suppression of CD4+CD25− T cells by cell–cell contact and not secretion of suppressor cytokines. In this study, we demonstrated that CD4+CD25+ T cells do produce high levels of transforming growth factor (TGF)-β1 and interleukin (IL)-10 compared with CD4+CD25− T cells when stimulated by plate-bound anti-CD3 and soluble anti-CD28 and/or IL-2, and secretion of TGF-β1 (but not other cytokines), is further enhanced by… Show more

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Cited by 1,467 publications
(1,205 citation statements)
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References 31 publications
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“…These results suggest that Smad3-dependent TGF-b signaling in effector CD4 + T cells is not required for CD4 + CD25 + Treg cell-mediated control of bacterial-driven mucosal inflammation. Some studies have suggested a correlation between Treg function and the expression of a latent, membranebound form of TGF-b1 on CD4 + CD25 + Treg cells [28][29][30]. While these studies promote the view that CD4 + CD25 + Treg cells act as carriers of TGF-b1 to activated effector T cells, the alternate view is that surface TGF-b1 may be bound to TGF-b-signaling To determine whether non-CD4 + CD25 + Treg cellderived TGF-b plays any role in suppressing the pathogenic potential of effector T cells, 1 Â 10 6 CD4 + CD25 -T cells were transferred alone into RAG2 -/-mice with or without the administration of a neutralizing anti-TGF-b antibody or an isotype control, and the recipients were monitored for the incidence and severity of IBD.…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…These results suggest that Smad3-dependent TGF-b signaling in effector CD4 + T cells is not required for CD4 + CD25 + Treg cell-mediated control of bacterial-driven mucosal inflammation. Some studies have suggested a correlation between Treg function and the expression of a latent, membranebound form of TGF-b1 on CD4 + CD25 + Treg cells [28][29][30]. While these studies promote the view that CD4 + CD25 + Treg cells act as carriers of TGF-b1 to activated effector T cells, the alternate view is that surface TGF-b1 may be bound to TGF-b-signaling To determine whether non-CD4 + CD25 + Treg cellderived TGF-b plays any role in suppressing the pathogenic potential of effector T cells, 1 Â 10 6 CD4 + CD25 -T cells were transferred alone into RAG2 -/-mice with or without the administration of a neutralizing anti-TGF-b antibody or an isotype control, and the recipients were monitored for the incidence and severity of IBD.…”
Section: Resultsmentioning
confidence: 99%
“…The most conclusive data on the role of Treg cell-derived suppressor cytokines has been obtained using IL-10 -/-CD4 + CD25 + T cells that fail both to suppress IBD induced by antigen-experienced effector T cells and to promote the chronic persistence of L. major in resistant C57BL/6 mice [9,10]. TGF-b has also been implicated in IBD, as the disease-protective effect of CD4 + CD45RB low or CD4 + CD25 + cells on CD4 + CD45RB high -induced colitis was abrogated by anti-TGF-b treatment [28,29]. The cellular source and targets of TGF-b in the effector phase of CD4 + CD25 + Treg activity has, however, remained elusive.…”
mentioning
confidence: 99%
“…6,7,26,27 These CD4 þ Tregs and CD8 þ Ti have been shown to inhibit autoimmunity through CD4 þ Treg-mediated cell-cell contact (dependent on Foxp3, cell surface GITR, and membrane bound TGFb) and CD8 þ Treg secretion of TGFb. [28][29][30][31] In an attempt to understand the mechanisms by which pCons mediates immune tolerance, we employed microarray technology to examine differences in gene expression profiles between naive BWF1 mice and BWF1 mice treated with pCons. Recently, microarray analyses has been used by other investigators to study differential gene expression patterns in SLE patients as compared with healthy controls.…”
Section: Introductionmentioning
confidence: 99%
“…Tregs can inhibit DCs through mechanisms 1 and 2, and Teff cells through mechanisms 1, 2, and 3. In the cell‐cell contact model, Tregs directly bind to the DCs or effector T cells through receptor‐ligand interactions, such as peptide‐major histocompatibility complex (pMHC)II‐TCR and CTLA4/B7‐1, and mediate inhibition, cytolysis, or apoptosis of the cells by delivering suppressive factors, such as cyclic adenosine monophosphate and transforming growth factor‐beta (TGFβ)1 via gap junctions48, 53, 54 or by membrane‐bound TGFβ. Next, in the inhibitory cytokine secretion model, Tregs upon activation can directly secrete IL‐10, TGFβ, and IL‐35 that mediate suppression of DCs and Teff cells 55, 56, 57.…”
Section: Immune System and Its Complexitymentioning
confidence: 99%
“…Tregs also inhibit B cell antibody production by secreting inhibitory factors IL‐10, TGFβ, and granzymes, or by binding through CTLA4/B7‐1 interaction 53. It has been shown that increased presence of Tregs decreases the production of antibodies, whereas their absence increases production 62, 63, 64.…”
Section: Immune System and Its Complexitymentioning
confidence: 99%