Skip navigation
Skip navigation

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

Chang, Pheh-Ping; Lee, Sau K; Hu, Xin; Davey, Gayle; Duan, Guowen; Cho, Jae-Ho; Karupiah, Guna; Sprent, Jonathan; Heath, William R; Bertram, Edward M; Vinuesa, Carola

Description

Tight regulation of virus-induced cytotoxic effector CD8+ T cells is essential to prevent immunopathology. Naturally occurring effector CD8+ T cells, with a KLRG1hi CD62Llo 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 (Roquinsan), effector...[Show more]

dc.contributor.authorChang, Pheh-Ping
dc.contributor.authorLee, Sau K
dc.contributor.authorHu, Xin
dc.contributor.authorDavey, Gayle
dc.contributor.authorDuan, Guowen
dc.contributor.authorCho, Jae-Ho
dc.contributor.authorKarupiah, Guna
dc.contributor.authorSprent, Jonathan
dc.contributor.authorHeath, William R
dc.contributor.authorBertram, Edward M
dc.contributor.authorVinuesa, Carola
dc.date.accessioned2014-02-20T03:59:10Z
dc.date.available2014-02-20T03:59:10Z
dc.identifier.issn0022-1767
dc.identifier.urihttp://hdl.handle.net/1885/11401
dc.description.abstractTight regulation of virus-induced cytotoxic effector CD8+ T cells is essential to prevent immunopathology. Naturally occurring effector CD8+ T cells, with a KLRG1hi CD62Llo 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 (Roquinsan), effector CD8+ T cells accumulate in a cell-autonomous manner, most prominently as SLEC-like effectors. Excessive IFN-y 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-y 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.
dc.description.sponsorshipThis work was supported by a Viertel Senior Medical Research Fellowship (to C.G.V.), National Health and Medical Research Council program grants (to C.G.V., J.S., and W.R.H.), and National Institutes of Health Contract BAA-NIAID-DAIT-07-35 (to E.M.B. and G.K.).
dc.format11 pages
dc.publisherAmerican Association of Immunologists
dc.rightshttp://www.sherpa.ac.uk/romeo/issn/0022-1767/Copyright 2012 by The American Association of Immunologists, Inc.
dc.sourceThe Journal of Immunology 189.2 (2012):701-710
dc.subjectIFN-y mRNA
dc.subjectrepression
dc.subjectt cells
dc.titleBreakdown in repression of IFN-y mRNA leads to accumulation of self-reactive effector CD8+ T cells
dc.typeJournal article
local.identifier.citationvolume189
dcterms.dateAccepted2012-05-07
dc.date.issued2012-06-08
local.identifier.absfor110704 - Cellular Immunology
local.identifier.absfor110703 - Autoimmunity
local.identifier.ariespublicationu9505948xPUB92
local.publisher.urlhttp://www.aai.org/
local.type.statusPublished Version
local.contributor.affiliationChang, Pheh-Ping, Department of Pathogens and Immunity, John Curtin School of Medical Research, Australian National University
local.contributor.affiliationLee, Sau K, Department of Pathogens and Immunity, John Curtin School of Medical Research, Australian National University
local.contributor.affiliationHu, Xin, Department of Pathogens and Immunity, John Curtin School of Medical Research, Australian National University
local.contributor.affiliationDuan, Guowen, Department of Pathogens and Immunity, John Curtin School of Medical Research, Australian National University
local.contributor.affiliationKarupiah, Guna, Department of Immunology, John Curtin School of Medical Research, Australian National University
local.contributor.affiliationBertram, Edward M, Department of Immunology, John Curtin School of Medical Research, Australian National University
local.contributor.affiliationVinuesa, Carola G, Department of Pathogens and Immunity, John Curtin School of Medical Research, Australian National University
local.bibliographicCitation.issue2
local.bibliographicCitation.startpage701
local.bibliographicCitation.lastpage710
local.identifier.doi10.4049/jimmunol.1102432
local.identifier.absseo920108 - Immune System and Allergy
local.identifier.absseo920104 - Diabetes
dc.date.updated2015-12-08T08:43:11Z
local.identifier.scopusID2-s2.0-84863623357
local.identifier.thomsonID000306119800028
CollectionsANU Research Publications

Download

There are no files associated with this item.


Items in Open Research are protected by copyright, with all rights reserved, unless otherwise indicated.

Updated:  19 May 2020/ Responsible Officer:  University Librarian/ Page Contact:  Library Systems & Web Coordinator