| First Author | Scheu S | Year | 2006 |
| Journal | Nat Immunol | Volume | 7 |
| Issue | 6 | Pages | 644-51 |
| PubMed ID | 16680145 | Mgi Jnum | J:112676 |
| Mgi Id | MGI:3662995 | Doi | 10.1038/ni1338 |
| Citation | Scheu S, et al. (2006) Activation of the integrated stress response during T helper cell differentiation. Nat Immunol 7(6):644-51 |
| abstractText | Adaptive immune responses require clonal expansion and differentiation of naive T cells into cytokine-secreting effector cells. After priming via signals through the T cell receptor, naive T helper cells express cytokine mRNA but do not secrete cytokine protein without additional T cell receptor stimulation. Here we show that primed T cells demonstrated phosphorylation of eukaryotic initiation factor 2-alpha (eIF2alpha), a 'collapsed' polysome profile, increased expression of stress-response genes and accumulation of cytoplasmic granules associated with RNA-binding proteins, all features of the integrated stress response. Restimulation of the cells resulted in rapid eIF2alpha dephosphorylation, ribosomal mRNA loading and cytokine secretion. Interference with the function of granule-associated proteins or accumulation of phosphorylated eIF2alpha enhanced release of interleukin 4 during T helper type 2 priming. Therefore, T lymphocytes require components of the integrated stress response to uncouple differentiation from the execution of effector functions. |
