Themis controls T cell activation, effector functions, and metabolism of peripheral CD8+ T cells
Abstract
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.
Related
- A pro-inflammatory effector-memory T cell program links peripheral EBV priming to CNS autoimmunity
- Structural and functional analysis of the cerato-platanin-like effector protein Cpl1 suggests diverging functions in smut fungi
- Cyclic tri-adenylate controls a CARF-TM effector in type II Panoptes anti-phage systems
- T-cell metabolic reprogramming in systemic lupus erythematosus: linking intracellular metabolism to effector differentiation and senescent-like/exhausted-like states
- One-carbon metabolism sustains effector T cell function through cell-surface glycosylation
BibTeX
@article{gautam2026themis,
title = {{Themis controls T cell activation, effector functions, and metabolism of peripheral CD8+ T cells}},
author = {Namrata Gautam and Lukasz Wojciech and Jiawei Yap and Yen Leong Chua and Eyan Mw Ding and Don Cn Sim and Alrina Sm Tan and Patricia J Ahl and Mukul Prasad and Desmond Wh Tung and John E Connolly and Giulia Adriani and Joanna Brzostek and Nicholas Rj Gascoigne},
journal = {Life Science Alliance},
year = {2026},
month = oct,
doi = {10.26508/lsa.202302156},
url = {https://hal.science/hal-05776439v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Themis controls T cell activation, effector functions, and metabolism of peripheral CD8+ T cells
AU - Namrata Gautam
AU - Lukasz Wojciech
AU - Jiawei Yap
AU - Yen Leong Chua
AU - Eyan Mw Ding
AU - Don Cn Sim
AU - Alrina Sm Tan
AU - Patricia J Ahl
AU - Mukul Prasad
AU - Desmond Wh Tung
AU - John E Connolly
AU - Giulia Adriani
AU - Joanna Brzostek
AU - Nicholas Rj Gascoigne
PY - 2026
DA - 2026/10/03
JO - Life Science Alliance
DO - 10.26508/lsa.202302156
UR - https://hal.science/hal-05776439v1
AB - 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.
SN - 2575-1077
ER -