| First Author | Iborra S | Year | 2013 |
| Journal | J Exp Med | Volume | 210 |
| Issue | 7 | Pages | 1463-79 |
| PubMed ID | 23776078 | Mgi Jnum | J:202288 |
| Mgi Id | MGI:5517778 | Doi | 10.1084/jem.20112495 |
| Citation | Iborra S, et al. (2013) N-ras couples antigen receptor signaling to Eomesodermin and to functional CD8+ T cell memory but not to effector differentiation. J Exp Med 210(7):1463-79 |
| abstractText | Signals from the TCR that specifically contribute to effector versus memory CD8(+) T cell differentiation are poorly understood. Using mice and adoptively transferred T lymphocytes lacking the small GTPase N-ras, we found that N-ras-deficient CD8(+) T cells differentiate efficiently into antiviral primary effectors but have a severe defect in generating protective memory cells. This defect was rescued, although only partly, by rapamycin-mediated inhibition of mammalian target of rapamycin (mTOR) in vivo. The memory defect correlated with a marked impairment in vitro and in vivo of the antigen-mediated early induction of T-box transcription factor Eomesodermin (Eomes), whereas T-bet was unaffected. Besides N-ras, early Eomes induction in vitro required phosphoinositide 3-kinase (PI3K)-AKT but not extracellular signal-regulated kinase (ERK) activation, and it was largely insensitive to rapamycin. Consistent with N-ras coupling Eomes to T cell memory, retrovirally enforced expression of Eomes in N-ras-deficient CD8(+) T cells effectively rescued their memory differentiation. Thus, our study identifies a critical role for N-ras as a TCR-proximal regulator of Eomes for early determination of the CD8(+) T cell memory fate. |
