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Title: PD-1+ memory phenotype CD4+ T cells expressing C/EBPα underlie T cell immunodepression in senescence and leukemia
Authors: Shimatani, Kenichiro
Nakashima, Yasuhiro
Hattori, Masakazu  kyouindb  KAKEN_id
Hamazaki, Yoko  kyouindb  KAKEN_id
Minato, Nagahiro  kyouindb  KAKEN_id
Author's alias: 湊, 長博
Issue Date: Sep-2009
Publisher: National Academy of Sciences
Journal title: Proceedings of the National Academy of Sciences.
Volume: 106
Issue: 37
Start page: 15807
End page: 15812
Abstract: Although altered T cell function plays a part in immunosenescence, the mechanisms remain uncertain. Here we identify a bona fide age-dependent PD-1+ memory phenotype (MP) CD4+ T cell subpopulation that hardly proliferates in response to T cell receptor (TCR) stimulation and produces abundant osteopontin at the cost of typical T cell lymphokines. These T cells demonstrate impaired repopulation in Rag2−/− mice, but a homeostatic proliferation in γ-ray–irradiated mice. These T cells also reveal a unique molecular signature, including a strong expression of C/EBPα normally expressed in myeloid-lineage cells, with diminished c-Myc and cyclin D1. Transduction of Cebpa in regular CD4+ T cells inhibited the TCR-mediated proliferation with c-Myc and cyclin D1 repression and caused a striking activation of Spp1 encoding osteopontin along with concomitant repression of T cell lymphokine genes. Although these T cells gradually increase in number with age and become predominant at the senescent stage in normal mice, the generation is robustly accelerated during leukemia. In both conditions, their predominance is associated with the diminution of specific CD4+ T cell response. The results suggest that global T cell immunodepression in senescence and leukemia is attributable to the increase in PD-1+ MP CD4+ T cells expressing C/EBPα.
Description: 免疫老化のメカニズムを解明しました. 京都大学プレスリリース. 2009-09-08.
Rights: c 2009 by the National Academy of Sciences
この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。This is not the published version. Please cite only the published version.
DOI(Published Version): 10.1073/pnas.0908805106
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