| First Author | Chang PP | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 2 | Pages | 701-10 |
| PubMed ID | 22685317 | Mgi Jnum | J:189550 |
| Mgi Id | MGI:5446099 | Doi | 10.4049/jimmunol.1102432 |
| Citation | Chang PP, et al. (2012) Breakdown in repression of IFN-gamma mRNA leads to accumulation of self-reactive effector CD8+ T cells. J Immunol 189(2):701-10 |
| abstractText | 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-gamma 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-gamma 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. |
