| First Author | Zhang L | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 2 | Pages | e30592 |
| PubMed ID | 22363451 | Mgi Jnum | J:224051 |
| Mgi Id | MGI:5661138 | Doi | 10.1371/journal.pone.0030592 |
| Citation | Zhang L, et al. (2012) TSC1/2 signaling complex is essential for peripheral naive CD8+ T cell survival and homeostasis in mice. PLoS One 7(2):e30592 |
| abstractText | The PI3K-Akt-mTOR pathway plays crucial roles in regulating both innate and adaptive immunity. However, the role of TSC1, a critical negative regulator of mTOR, in peripheral T cell homeostasis remains elusive. With T cell-specific Tsc1 conditional knockout (Tsc1 KO) mice, we found that peripheral naive CD8(+) T cells but not CD4(+) T cells were severely reduced. Tsc1 KO naive CD8(+) T cells showed profound survival defect in an adoptive transfer model and in culture with either stimulation of IL-7 or IL-15, despite comparable CD122 and CD127 expression between control and KO CD8(+) T cells. IL-7 stimulated phosphorylation of Akt(S473) was diminished in Tsc1 KO naive CD8(+)T cells due to hyperactive mTOR-mediated feedback suppression on PI3K-AKT signaling. Furthermore, impaired Foxo1/Foxo3a phosphorylation and increased pro-apoptotic Bim expression in Tsc1 KO naive CD8(+)T cells were observed upon stimulation of IL-7. Collectively, our study suggests that TSC1 plays an essential role in regulating peripheral naive CD8(+) T cell homeostasis, possible via an mTOR-Akt-FoxO-Bim signaling pathway. |
