TGF-β Induces Foxp3 + T-Regulatory Cells from CD4 + CD25 − Precursors

Fu, Shuang; Zhang, Nan; Yopp, Adam C.; Chen, Dongmei; Mao, Minwei; Chen, Dan; Zhang, Haojiang; Ding, Yaozhong; Bromberg, Jonathan S.

doi:10.1111/j.1600-6143.2004.00566.x

Cited by 477 publications

(364 citation statements)

References 51 publications

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“…37 TGF-b was reported by several groups to induce CD4 þ CD25 þ T cells endowed with regulatory functions. [13][14][15] Several CD4 þ CD25 þ T-cell subsets have been described to exert regulatory functions. [2][3][4] Sagakuchi's group first demonstrated that CD4 þ T cells expressing CD25 molecules controlled autoimmunity in naive mice.…”

Section: Discussionmentioning

confidence: 99%

“…Regulatory CD4 þ T cells induced by in vitro TGF-b exposure arise from 'conventional' naive CD4 þ CD25 À T-cell precursors. [13][14][15] They acquire Foxp3 mRNA expression and exert their suppressive activity mainly through TGF-b. [13][14][15] In our study, despite TGF-b dependency of Treg induction, such cells induced after apoptotic cell infusion expressed high levels of Foxp3 mRNA and exerted ex vivo suppressive activities mainly through a cell contact-dependent activity.…”

Section: Discussionmentioning

confidence: 99%

“…administration of apoptotic spleen cells, simultaneously with BM grafts, favored engraftment via a TGF-b-dependent mechanism. 35 As TGF-b can be implicated in the generation of Treg subpopulations, 9,[13][14][15] and as fluorescent apoptotic bodies within splenic phagocytes could be found (Figure 1a), we first analyzed the spleen for the presence of CD4 þ CD25 þ T cells at weeks 7-9 post-BMT. Analysis of splenic T-cell populations in mice given apoptotic cells revealed a CD4 þ CD25 þ T-cell increase in engrafted versus nonengrafted recipients (8.870.6 versus 3.970.4%, mean7S.E.M., 10 mice per group, Po0.01, Figure 2a).…”

Section: IV Apoptotic Spleen Cell Infusion Leads To the Tgf-mentioning

confidence: 99%

“…4,5 Recently, forkhead-box transcription factor p3 (Foxp3, called also scurfin) has emerged as an adequate marker for 'natural' CD4 þ CD25 þ 'suppressive' T cells [10][11][12] as well as other peripherally produced CD4 þ T cells endowed with regulatory properties. [13][14][15] However, the phenotypic characterization as well as suppressive mechanism of CD4 þ Treg cells may differ, depending on the experimental model used. 3 Apoptosis is a physiological process that liberates intracellular proteins, rendering critical the maintenance of selftolerance.…”

Section: Introductionmentioning

confidence: 99%

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Intravenous apoptotic spleen cell infusion induces a TGF-β-dependent regulatory T-cell expansion

et al. 2005

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Apoptotic leukocytes are endowed with immunomodulatory properties that can be used to enhance hematopoietic engraftment and prevent graft-versus-host disease (GvHD). This apoptotic cell-induced tolerogenic effect is mediated by host macrophages and not recipient dendritic cells or donor phagocytes present in the bone marrow graft as evidenced by selective cell depletion and trafficking experiments. Furthermore, apoptotic cell infusion is associated with TGF-bdependent donor CD4 þ CD25 þ T-cell expansion. Such cells have a regulatory phenotype (CD62L high and intracellular CTLA-4 þ ), express high levels of forkhead-box transcription factor p3 (Foxp3) mRNA and exert ex vivo suppressive activity through a cell-to-cell contact mechanism. In vivo CD25 depletion after apoptotic cell infusion prevents the apoptotic cell-induced beneficial effects on engraftment and GvHD occurrence. This highlights the role of regulatory T cells in the tolerogenic effect of apoptotic cell infusion. This novel association between apoptosis and regulatory T-cell expansion may also contribute to preventing deleterious autoimmune responses during normal turnover.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: IV Apoptotic Spleen Cell Infusion Leads To the Tgf-mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Intravenous apoptotic spleen cell infusion induces a TGF-β-dependent regulatory T-cell expansion

et al. 2005

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“…Studies have reported that TGF-has the ability to induce CD4 + CD25 -cells to become CD4 + CD25 + Tregs in vitro [52,53], and TGF-can induce FoxP3 expression in iTregs [54,55]. Additionally, other studies have clearly demonstrated that the suppressive capacity of FoxP3 + Tregs in vivo is via a TGF--dependent mechanism [56,57].…”

Section: Transforming Growth Factor-mentioning

confidence: 99%

Regulatory T cells in vitiligo: Implications for pathogenesis and therapeutics

Dwivedi

Kemp

Laddha

et al. 2015

Autoimmunity Reviews

101

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Vitiligo is a hypomelanotic autoimmune skin disease arising from a breakdown in immunological self-tolerance, which leads to aberrant immune responses against melanocytes.Regulatory T cells (Tregs) are crucial to the development of self-tolerance and so are major foci in the study of autoimmune pathogenesis of vitiligo. This review will summarise recent findings concerning the role of Tregs in the pathogenesis of vitiligo. In addition, as antigen-specific Tregs are a potential route for the reinstatement of immune tolerance, new strategies that expand or induce de novo generation of Tregs and which are currently being investigated as therapies for other autoimmune diseases, will be discussed. These approaches will highlight the opportunities for Treg cell-based therapeutics in vitiligo.4

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