AUTHOR=Kamimura Daisuke , Atsumi Toru , Stofkova Andrea , Nishikawa Naoki , Ohki Takuto , Suzuki Hironao , Katsunuma Kokichi , Jiang Jing-jing , Bando Hidenori , Meng Jie , Sabharwal Lavannya , Ogura Hideki , Hirano Toshio , Arima Yasunobu , Murakami Masaaki TITLE=Naïve T Cell Homeostasis Regulated by Stress Responses and TCR Signaling JOURNAL=Frontiers in Immunology VOLUME=6 YEAR=2015 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2015.00638 DOI=10.3389/fimmu.2015.00638 ISSN=1664-3224 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.