High Self-reactivity Drives T-bet and Potentiates Treg Function in Tissue-specific Autoimmunity

Overview

Journal JCI Insight

Specialties Biomedical Engineering
General Medicine

Date 2018 Jan 26

PMID 29367462

Citations 29

Authors

Maran L Sprouse

Marissa A Scavuzzo

Samuel Blum

Ivan Shevchenko

Thomas Lee

George Makedonas

Malgorzata Borowiak

Matthew L Bettini

Maria Bettini

Affiliations

Soon will be listed here.

Abstract

T cell receptor (TCR) affinity is a critical factor of Treg lineage commitment, but whether self-reactivity is a determining factor in peripheral Treg function remains unknown. Here, we report that a high degree of self-reactivity is crucial for tissue-specific Treg function in autoimmunity. Based on high expression of CD5, we identified a subset of self-reactive Tregs expressing elevated levels of T-bet, GITR, CTLA-4, and ICOS, which imparted significant protection from autoimmune diabetes. We observed that T-bet expression in Tregs, necessary for control of Th1 autoimmunity, could be induced in an IFNγ-independent fashion and, unlike in conventional T cells (Tconv), was strongly correlated with the strength of TCR signaling. The level of CD5 similarly identified human Tregs with an increased functional profile, suggesting that CD5hi Tregs may constitute an efficacious subpopulation appropriate for use in adoptive Treg therapies for treatment of inflammatory conditions. Overall, this work establishes an instrumental role of high TCR self-reactivity in driving Treg function.

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