Suppressive properties of human CD4<sup>+</sup>CD25<sup>+</sup> regulatory T cells are dependent on CTLA‐4 expression

Birebent, Brigitte; Lorho, R.; Lechartier, Hélène; Guibert, Sophie de; Alizadeh, Mehdi; Vu, Nicolas; Beauplet, A.; Robillard, Nelly; Sémana, G.

doi:10.1002/eji.200324632

Cited by 109 publications

(94 citation statements)

References 39 publications

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“…CD40 expression during EAE has been shown to be necessary for B7 induction (4), and B cells receiving CD40 costimulation in the absence of BCR signaling have been shown to produce . We propose that this B cell then interacts with and activates a CD4 ϩ CD25 ϩ Treg cells via B7/ CTLA-4 (37,38). The Treg cells then migrate into the CNS and suppress inflammation via an IL-10-dependent mechanism (13,46).…”

Section: Discussionmentioning

confidence: 99%

“…The B7 molecules have two known ligands, CD28 and CTLA-4, both expressed by a variety of T cell populations including Treg cells (34). Although the precise role of B7.1 and B7.2 in immune regulation is not known, evidence has emerged to support a role for B7.1 in Treg cell function (35,36), as well as CTLA-4 (37,38). In EAE, the absence of both B7.1 and B7.2 reduced the severity of disease (5).…”

Section: Discussionmentioning

confidence: 99%

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B Cell Regulation of CD4+CD25+ T Regulatory Cells and IL-10 Via B7 is Essential for Recovery From Experimental Autoimmune Encephalomyelitis

Mann

Maresz

Shriver

et al. 2007

The Journal of Immunology

274

219

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CD4+CD25+ T regulatory (Treg) cells expressing the Foxp3 transcription factor have been shown to be present in the CNS during the autoimmune disease experimental autoimmune encephalomyelitis (EAE) and can inhibit EAE clinical disease by an IL-10-dependent mechanism. In addition, IL-10 expression in the CNS late in the EAE disease course has been attributed to recovery. However, it is not known how Treg cells and IL-10 expressions are regulated during EAE. We have previously shown a requirement for B cells in recovery from EAE and here investigated whether this was due to a deficiency in Treg cells and IL-10 in the CNS. We found that B cell deficiency resulted in a delay in the emergence of Foxp3-expressing Treg cells and IL-10 in the CNS during EAE, but not in the periphery. Reconstitution with wild-type B cells resulted in disease recovery and normalized IL-10 and Foxp3 expression. However, reconstitution with B7-deficient B cells did not. Furthermore, we show that IL-10 and Foxp3 expression is enhanced in CNS nonencephalitogenic T cells. These data suggest a novel mechanism whereby B cells regulate CD4+CD25+ Treg cells via B7 and subsequently enter the CNS and suppress autoimmune inflammation, mediating recovery.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

B Cell Regulation of CD4+CD25+ T Regulatory Cells and IL-10 Via B7 is Essential for Recovery From Experimental Autoimmune Encephalomyelitis

Mann

Maresz

Shriver

et al. 2007

The Journal of Immunology

274

219

View full text Add to dashboard Cite

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“…In this interaction, costimulatory molecules such as CD86/CD80 on the antigen-presenting cells (APCs) and CD28/CTLA-4 on the T cell are critical players. CTLA-4 on CD4ϩ,CD25ϩ Treg cells has been reported to be essential for suppression (17)(18)(19). CD28 signaling is important as well, since CD28 -/-mice lack functional CD4ϩ,CD25ϩ Treg cells (20).…”

mentioning

confidence: 99%

Proinflammatory mediator–induced reversal of CD4+,CD25+ regulatory T cell–mediated suppression in rheumatoid arthritis

Amelsfort¹,

Roon²,

Noordegraaf³

et al. 2007

Arthritis & Rheumatism

167

123

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Objective. We previously demonstrated that CD4؉,CD25؉ regulatory T (Treg) cells are present in increased numbers in the synovial fluid (SF) of rheumatoid arthritis (RA) patients and display enhanced suppressive activity as compared with their peripheral blood (PB) counterparts. Despite the presence of these immunoregulatory cells in RA, chronic inflammation persists. The purpose of the present study was to investigate whether particular proinflammatory mediators that are associated with RA could abrogate CD4؉,CD25؉ Treg-mediated suppression.Methods.

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“…In the human system, CTLA4 þ T reg cells display a stronger suppressive activity in vitro than CTLA4 À T reg cells. 25 However, CTLA4 is not essential for the development and function of T reg cells, since its loss could be compensated by increased secretion of IL10 and TGF-b by CTLA4 À CD4 þ CD25 þ T reg cells. 26 The conversion of murine naïve nonregulatory CD4 þ CD25 À T cells into T reg cells by retroviral overexpression of FOXP3 underlines the master control function of this transcription factor.…”

mentioning

confidence: 99%

UBD, a downstream element of FOXP3, allows the identification of LGALS3, a new marker of human regulatory T cells

Ocklenburg

Moharregh-Khiabani

Geffers

et al. 2006

Laboratory Investigation

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Here, we report the identification of the ubiquitin-like gene UBD as a downstream element of FOXP3 in human activated regulatory CD4 þ CD25 hi T cells (T reg ). Retroviral transduction of UBD in human allo-reactive effector CD4 þ T helper (T h ) cells upregulates CD25 and mediates downregulation of IL4 and IL5 expression similar to overexpression of FOXP3. Moreover, UBD impairs T h cell proliferation without upregulation of FOXP3 and impairs calcium mobilization. In the presence of ionomycin, overexpression of UBD in T h cells leads to the induction of IL1R2 that resemble FOXP3-transduced T h cells and naturally derived T reg cells. A comparison of the transcriptome of FOXP3-and UBD-transduced T h cells with T reg cells allowed the identification of the gene LGALS3. However, high levels of LGALS3 protein expression were observed only in human CD4 þ CD25 hi derived T reg cells and FOXP3-transduced T h cells, whereas little was induced in UBD-transduced T h cells. Thus, UBD contributes to the anergic phenotype of human regulatory T cells and acts downstream in FOXP3 induced regulatory signaling pathways, including regulation of LGALS3 expression. High levels of LGALS3 expression represent a FOXP3-signature of human antigen-stimulated CD4 þ CD25 hi derived regulatory T cells.

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Suppressive properties of human CD4⁺CD25⁺ regulatory T cells are dependent on CTLA‐4 expression

Abstract: It has been demonstrated that T cells with regulatory properties are present within the peripheral blood CD4

Cited by 109 publications

References 39 publications

B Cell Regulation of CD4+CD25+ T Regulatory Cells and IL-10 Via B7 is Essential for Recovery From Experimental Autoimmune Encephalomyelitis

B Cell Regulation of CD4+CD25+ T Regulatory Cells and IL-10 Via B7 is Essential for Recovery From Experimental Autoimmune Encephalomyelitis

Proinflammatory mediator–induced reversal of CD4+,CD25+ regulatory T cell–mediated suppression in rheumatoid arthritis

UBD, a downstream element of FOXP3, allows the identification of LGALS3, a new marker of human regulatory T cells

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Suppressive properties of human CD4+CD25+ regulatory T cells are dependent on CTLA‐4 expression

Abstract: It has been demonstrated that T cells with regulatory properties are present within the peripheral blood CD4

Cited by 109 publications

References 39 publications

B Cell Regulation of CD4+CD25+ T Regulatory Cells and IL-10 Via B7 is Essential for Recovery From Experimental Autoimmune Encephalomyelitis

B Cell Regulation of CD4+CD25+ T Regulatory Cells and IL-10 Via B7 is Essential for Recovery From Experimental Autoimmune Encephalomyelitis

Proinflammatory mediator–induced reversal of CD4+,CD25+ regulatory T cell–mediated suppression in rheumatoid arthritis

UBD, a downstream element of FOXP3, allows the identification of LGALS3, a new marker of human regulatory T cells

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Suppressive properties of human CD4⁺CD25⁺ regulatory T cells are dependent on CTLA‐4 expression