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dc.contributor.authorShimatani, Kenichiroja
dc.contributor.authorNakashima, Yasuhiroja
dc.contributor.authorHattori, Masakazuja
dc.contributor.authorHamazaki, Yokoja
dc.contributor.authorMinato, Nagahiroja
dc.contributor.alternative湊, 長博ja
dc.date.accessioned2009-10-27T05:01:45Z-
dc.date.available2009-10-27T05:01:45Z-
dc.date.issued2009-09ja
dc.identifier.issn0027-8424ja
dc.identifier.urihttp://hdl.handle.net/2433/86175-
dc.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. http://www.kyoto-u.ac.jp/ja/news_data/h/h1/news6/2009/090908_1.htmja
dc.description.abstractAlthough 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.ja
dc.language.isoengja
dc.publisherNational Academy of Sciencesja
dc.rightsc 2009 by the National Academy of Sciencesja
dc.rights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.ja
dc.titlePD-1+ memory phenotype CD4+ T cells expressing C/EBPα underlie T cell immunodepression in senescence and leukemiaja
dc.type.niitypeJournal Articleja
dc.identifier.jtitleProceedings of the National Academy of Sciences.ja
dc.identifier.volume106ja
dc.identifier.issue37ja
dc.identifier.spage15807ja
dc.identifier.epage15812ja
dc.relation.doi10.1073/pnas.0908805106ja
dc.textversionauthorja
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