@article{d46b14338c6b4a2eb8b21da26e5b940e,
title = "Dysfunction of CD8 + PD-1 + T cells in type 2 diabetes caused by the impairment of metabolism-immune axis",
abstract = "The metabolic changes and dysfunction in CD8 + T cells may be involved in tumor progression and susceptibility to virus infection in type 2 diabetes (T2D). In C57BL/6JJcl mice fed with high fat-high sucrose chow (HFS), multifunctionality of CD8 + splenic and tumor-infiltrating lymphocytes (TILs) was impaired and associated with enhanced tumor growth, which were inhibited by metformin. In CD8 + splenic T cells from the HFS mice, glycolysis/basal respiration ratio was significantly reduced and reversed by metformin. In the patients with T2D (DM), multifunctionality of circulating CD8 + PD-1 + T cells stimulated with PMA/ionomycin as well as with HLA-A*24:02 CMV peptide was dampened, while metformin recovered multifunctionality. Both glycolysis and basal respiration were reduced in DM, and glycolysis was increased by metformin. The disturbance of the link between metabolism and immune function in CD8 + PD-1 + T cells in T2D was proved by recovery of antigen-specific and non-specific cytokine production via metformin-mediated increase in glycolytic activity.",
author = "Ichiro Nojima and Shingo Eikawa and Nahoko Tomonobu and Yoshiko Hada and Nobuo Kajitani and Sanae Teshigawara and Satoshi Miyamoto and Atsuhito Tone and Uchida, {Haruhito A.} and Atsuko Nakatsuka and Jun Eguchi and Kenichi Shikata and Heiichiro Udono and Jun Wada",
note = "Funding Information: This work is supported by JSPS Grant-in-Aid for Scientific Research (B) Grant Number 19H03675 and Junior Scientist Development Grant by The Japan Diabetes Society. Funding Information: Haruhito A. Uchida belongs to the Department of Chronic Kidney Disease and Cardiovascular Disease which is endowed by Kawanishi Holdings, Chugai pharmaceutical, Boehringer Ingelheim and Terumo Corporation. Jun Wada receives speaker honoraria from Astellas, Astra Zeneca, Boeringer Ingelheim Japan, Daiichi Sankyo, MSD, Novartis, Tanabe Mitsubishi, Taisho Toyama and receives grant support from Bayer, Baxter, Chugai, Dainippon Sumitomo, Kyowa Hakko Kirin, MSD, Novartis, Novo Nordisk, Ono, Takeda, Tanabe Mitsubishi, Teijin. Other authors have no competing interests. Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41598-020-71946-3",
language = "English",
volume = "10",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}
