Therapeutic regulatory T cells subvert effector T cell function in inflamed islets to halt autoimmune diabetes

The Journal of Immunology : Official Journal of the American Association of Immunologists
Ashley E MahneQ Tang

Abstract

Therapeutic regulatory T cells (Tregs) can reverse pre-established autoimmune pathology. In this study, using a mouse model of autoimmune diabetes, we aimed to determine the means by which therapeutic Tregs control islet inflammation. Islet Ag-specific Tregs infiltrated inflamed islets soon after infusion into prediabetic mice, which was quickly followed by a selective reduction of mRNA associated with effector T cells in the islets. This change was partially due to decreased CD8(+) T cell accumulation in the tissue. CD8(+) T cells that remained in the islets after Treg treatment were able to engage dendritic cells in a manner similar to that found in untreated mice, consistent with the retention of an activated phenotype by islet dendritic cells shortly after Treg treatment. Nonetheless, Treg treatment abrogated IFN-γ production by intraislet CD8(+) and CD4(+) T cells at the protein level with minimal effect on IFN-γ mRNA. Sustained expression of IFN-γ protein by effector T cells was dependent on common γ-chain cytokine activation of the mTOR pathway, which was suppressed in islet CD8(+) T cells in vivo after Treg treatment. These multifaceted mechanisms underlie the efficacy of therapeutic Treg subversion of effector T cell f...Continue Reading

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Citations

Nov 26, 2015·Immunotherapy·Mei Zhang, Qizhi Tang
Apr 15, 2017·Molecular Therapy : the Journal of the American Society of Gene Therapy·Christian MuellerTerence R Flotte
Aug 26, 2017·Proceedings of the National Academy of Sciences of the United States of America·James F MohanChristophe Benoist
May 28, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Joanna E KlementowiczQizhi Tang
Oct 4, 2017·Frontiers in Immunology·James S YoungAnita S Chong
Apr 27, 2019·Frontiers in Immunology·Emeka B Okeke, Jude E Uzonna
Dec 21, 2017·Frontiers in Endocrinology·Adam L BurrackBrian T Fife
May 13, 2021·Human Gene Therapy·Weidong QinXiao Meng
Feb 13, 2020·Journal of Agricultural and Food Chemistry·Lingling JiaLi-Long Pan

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