Title |
Naïve T Cell Homeostasis Regulated by Stress Responses and TCR Signaling
|
---|---|
Published in |
Frontiers in immunology, December 2015
|
DOI | 10.3389/fimmu.2015.00638 |
Pubmed ID | |
Authors |
Daisuke Kamimura, Toru Atsumi, Andrea Stofkova, Naoki Nishikawa, Takuto Ohki, Hironao Suzuki, Kokichi Katsunuma, Jing-jing Jiang, Hidenori Bando, Jie Meng, Lavannya Sabharwal, Hideki Ogura, Toshio Hirano, Yasunobu Arima, Masaaki Murakami |
Abstract |
The survival of naïve T cells is believed to require signals from TCR-pMHC interactions and cytokines such as IL-7. In contrast, signals that negatively impact naïve T cell survival are less understood. We conducted a forward genetic screening of mice and found a mutant mouse line with reduced number of naïve T cells (T-Red mice). T-Red mice have a point mutation in the Kdelr1 gene, and their naïve T cells show enhanced integrated stress response (ISR), which eventually induces their apoptosis. Therefore, naïve T cells require a KDEL receptor-mediated mechanism that efficiently relieves cellular stress for their survival in vivo. Interestingly, naïve T cells expressing TCR with higher affinity/avidity to self-antigens survive in T-Red mice, suggesting the possible link between TCR-mediated survival and ISR-induced apoptosis. In this article, we discuss the regulation of naïve T cell homeostasis, keeping special attention on the ISR and TCR signal. |
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