Translation Control in CD4 T Cell Activation enforced by T-regulatory cells

Increased protein synthesis is a hallmark of CD4 effector T cell (Teff) activation. Regulatory T cells (Tregs) suppress the activation, proliferation, and subsequent effector functions of Teff cells. Several mechanisms have been proposed for Treg-mediated suppression, including release of suppressive cytokines and expression of inhibitory receptors. However, molecular mechanisms that enforce suppression on Teff cell function are unclear. Control of CD4 effector T cell activation has largely been defined at the transcriptional level, which does not reflect changes in post-transcriptional control. We Tregs suppress CD4 Teff activation through regulation of global protein synthesis prior to cell division. Using polysome profiling, we analyzed genome-wide changes in the transcriptome and translatome of activated CD4 Teff cells. We found that mRNAs encoding for the protein synthesis machinery are regulated at the level of translation in activated Teff cells, and that Tregs their translation without affecting their transcription. This translational inhibition is controlled by Treg-mediated regulation of Torc1 signaling. These data show that peripheral tolerance is enforced by Tregs through mRNA translational control in Teff cells. 75 samples total. 9 mice; 5 RiboTag mice (per mouse: Ribo IP and Input, 3 stimulations), 4 C57/B6 mice (per mouse: Polysomal, Subpolysomal, Input. 4 stimulations with some missing)