title: Activation of the integrated stress response during T helper cell differentiation.
abstract: 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.
authors: Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143, USA.
authors: Stefanie
authors: S
authors: Scheu
authors: Daniel B
authors: DB
authors: Stetson
authors: R Lee
authors: RL
authors: Reinhardt
authors: Jess H
authors: JH
authors: Leber
authors: Markus
authors: M
authors: Mohrs
authors: Richard M
authors: RM
authors: Locksley