TGF-beta Signaling is Required for the Function of Insulin-reactive T Regulatory Cells

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2006 May 4

PMID 16670772

Citations 20

Authors

Wei Du

F Susan Wong

Ming O Li

Jian Peng

Hao Qi

Richard A Flavell

Robert Sherwin

Li Wen

Affiliations

Soon will be listed here.

Abstract

We have previously isolated insulin-reactive Tregs from diabetic NOD mice designated 2H6, from which TCR transgenic mice were generated. The T cells from these 2H6 transgenic mice recognize insulin but have suppressive properties in vitro. They protect NOD mice in vivo from spontaneous development of diabetes and adoptive transfer of disease caused by polyclonal diabetogenic spleen cells as well as the highly diabetogenic monoclonal BDC2.5 TCR transgenic T cells that recognize an islet granule antigen. Using cells from both NOD and BDC2.5 mice that express a dominant-negative TGF-beta receptor type II (TGF-betaDNRII), we show that 2H6 T cells protected from disease by producing TGF-beta and that the ability of the target diabetogenic T cells to respond to TGF-beta was crucial. We further demonstrate that TGF-beta signaling in 2H6 cells was important for their protective properties, as 2H6 cells were unable to protect from adoptive transfer-induced diabetes if they were unable to respond to TGF-beta. Thus, our data demonstrate that insulin-specific regulatory cells protect from diabetes by virtue of their production of TGF-beta1 that acts in an autocrine manner to maintain their regulatory function and acts in a paracrine manner on the target cells.

Citing Articles

Bone Morphogenetic Proteins Shape T Cells.

Kraj P Front Immunol. 2022; 13:865546.

PMID: 35418975 PMC: 8995768. DOI: 10.3389/fimmu.2022.865546.

Insulin-Reactive T Cells Convert Diabetogenic Insulin-Reactive VH125 B Cells Into Tolerogenic Cells by Reducing Germinal Center T:B Cell Interactions in NOD Mice.

Pearson J, Li Y, Majewska-Szczepanik M, Guo J, Zhang L, Liu Y Front Immunol. 2020; 11:585886.

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A Novel Liposome Formulation Carrying Both an Insulin Peptide and a Ligand for Invariant Natural Killer T Cells Induces Accumulation of Regulatory T Cells to Islets in Nonobese Diabetic Mice.

Akimoto H, Fukuda-Kawaguchi E, Duramad O, Ishii Y, Tanabe K J Diabetes Res. 2019; 2019:9430473.

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Understanding Autoimmune Diabetes through the Prism of the Tri-Molecular Complex.

Bettini M, Bettini M Front Endocrinol (Lausanne). 2018; 8:351.

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Immunoregulation by members of the TGFβ superfamily.

Chen W, Ten Dijke P Nat Rev Immunol. 2016; 16(12):723-740.

PMID: 27885276 DOI: 10.1038/nri.2016.112.

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