Journal Article

Themis controls T cell activation, effector functions, and metabolism of peripheral CD8 + T cells

Ding, Eyan MW, Wojciech, Lukasz, Brzostek, Joanna, Gautam, Namrata, Yap, Jiawei, Sim, Don CN, Tung, Desmond WH, Adriani, Giulia, Chua, Yen Leong, Ahl, Patricia J, Connolly, John E, Gascoigne, Nicholas RJ, Prasad, Mukul, Tan, Alrina SM

2023

Overview

Themis is important in regulating positive selection of thymocytes during T cell development, but its role in peripheral T cells is less understood. Here, we investigated T cell activation and its sequelae using a tamoxifen-mediated, acute Themis deletion mouse model. We find that proliferation, effector functions including anti-tumor killing, and up-regulation of energy metabolism are severely compromised. This study reveals the phenomenon of peripheral adaptation to loss of Themis, by demonstrating direct TCR-induced defects after acute deletion of Themis that were not evident in peripheral T cells chronically deprived of Themis in dLck-Cre deletion model. Peripheral adaptation to long-term loss was compared using chronic versus acute tamoxifen-mediated deletion and with the (chronic) dLck-Cre deletion model. We found that upon chronic tamoxifen-mediated Themis deletion, there was modulation in the gene expression profile for both TCR and cytokine signaling pathways. This profile overlapped with (chronic) dLck-Cre deletion model. Hence, we found that peripheral adaptation induced changes to both TCR and cytokine signaling modules. Our data highlight the importance of Themis in the activation of CD8 + T cells.

• Publisher: Life Science Alliance,Life Science Alliance LLC
• Subject: Adaptation / Animals / CD8 antigen / CD8-Positive T-Lymphocytes / Cell activation / Clonal selection / Complications / Cytokines / Energy Metabolism / Gene deletion / Gene expression / Genotype & phenotype / Lymphocytes / Lymphocytes T / Metabolism / Mice / Peptides / Phosphatase / Positive selection / Proteins / Receptors, Antigen, T-Cell - genetics / T cell receptors / Tamoxifen / Tamoxifen - pharmacology / Thymocytes