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Breakdown in repression of IFN-γ mRNA leads to accumulation of self-reactive effector CD8+ T cells

Citation

Chang, PP and Lee, SK and Hu, X and Davey, G and Duan, G and Cho, JH and Karupiah, G and Sprent, J and Heath, WR and Bertram, EM and Vinuesa, CG, Breakdown in repression of IFN-γ mRNA leads to accumulation of self-reactive effector CD8+ T cells, Journal of Immunology, 189, (2) pp. 701-10. ISSN 0022-1767 (2012) [Refereed Article]

Copyright Statement

2012 by The American Association of Immunologists, Inc. All rights reserved.

DOI: doi:10.4049/jimmunol.1102432

Abstract

Tight regulation of virus-induced cytotoxic effector CD8(+) T cells is essential to prevent immunopathology. Naturally occurring effector CD8(+) T cells, with a KLRG1(hi) CD62L(lo) phenotype typical of short-lived effector CD8(+) T cells (SLECs), can be found in increased numbers in autoimmune-prone mice, most notably in mice homozygous for the san allele of Roquin. These SLEC-like cells were able to trigger autoimmune diabetes in a susceptible background. When Roquin is mutated (Roquin(san)), effector CD8(+) T cells accumulate in a cell-autonomous manner, most prominently as SLEC-like effectors. Excessive IFN-γ promotes the accumulation of SLEC-like cells, increases their T-bet expression, and enhances their granzyme B production in vivo. We show that overexpression of IFN-γ was caused by failed posttranscriptional repression of Ifng mRNA. This study identifies a novel mechanism that prevents accumulation of self-reactive cytotoxic effectors, highlighting the importance of regulating Ifng mRNA stability to maintain CD8(+) T cell homeostasis and prevent CD8-mediated autoimmunity.

Item Details

Item Type:Refereed Article
Keywords:IFN gamma, CD8 T lymphocytes, Autoimmunity
Research Division:Medical and Health Sciences
Research Group:Immunology
Research Field:Autoimmunity
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Immune System and Allergy
Author:Karupiah, G (Associate Professor Guna Karupiah)
ID Code:107811
Year Published:2012
Web of Science® Times Cited:15
Deposited By:Medicine (Discipline)
Deposited On:2016-03-24
Last Modified:2017-11-07
Downloads:0

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