| First Author | Staron MM | Year | 2014 |
| Journal | Immunity | Volume | 41 |
| Issue | 5 | Pages | 802-14 |
| PubMed ID | 25464856 | Mgi Jnum | J:323792 |
| Mgi Id | MGI:6838917 | Doi | 10.1016/j.immuni.2014.10.013 |
| Citation | Staron MM, et al. (2014) The transcription factor FoxO1 sustains expression of the inhibitory receptor PD-1 and survival of antiviral CD8(+) T cells during chronic infection. Immunity 41(5):802-14 |
| abstractText | Protein kinase B (also known as AKT) and the mechanistic target of rapamycin (mTOR) are central regulators of T cell differentiation, proliferation, metabolism, and survival. Here, we show that during chronic murine lymphocytic choriomeningitis virus infection, activation of AKT and mTOR are impaired in antiviral cytotoxic T lymphocytes (CTLs), resulting in enhanced activity of the transcription factor FoxO1. Blockade of inhibitory receptor programmed cell death protein 1 (PD-1) in vivo increased mTOR activity in virus-specific CTLs, and its therapeutic effects were abrogated by the mTOR inhibitor rapamycin. FoxO1 functioned as a transcriptional activator of PD-1 that promoted the differentiation of terminally exhausted CTLs. Importantly, FoxO1-null CTLs failed to persist and control chronic viral infection. Collectively, this study shows that CTLs adapt to persistent infection through a positive feedback pathway (PD-1?FoxO1?PD-1) that functions to both desensitize virus-specific CTLs to antigen and support their survival during chronic viral infection. |
