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Breakdown in repression of IFN-γ mRNA leads to accumulation of self-reactive effector CD8+ T cells
journal contribution
posted on 2023-05-18, 18:19 authored by Chang, PP, Lee, SK, Hu, X, Davey, G, Duan, G, Cho, JH, Gunasegaran KarupiahGunasegaran Karupiah, Sprent, J, Heath, WR, Bertram, EM, Vinuesa, CGTight 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.
History
Publication title
Journal of ImmunologyVolume
189Pagination
701-10ISSN
0022-1767Department/School
Tasmanian School of MedicinePublisher
Amer Assoc ImmunologistsPlace of publication
United StatesRights statement
© 2012 by The American Association of Immunologists, Inc. All rights reserved.Repository Status
- Restricted