サトウ カヨコ   SATO Kayoko
  佐藤 加代子
   所属   医学部 医学科(東京女子医科大学病院)
   職種   准教授
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 PSGL-1 expressing CD4 T cells contribute plaque instability in acute coronary syndrome.
掲載誌名 正式名:Circulation
略  称:Circulation
ISSNコード:00097322/15244539
掲載区分国外
出版社 American Heart Association, Inc.
巻・号・頁 124(21),Abstract 15412頁
著者・共著者 SATO Kayoko†, FUKUSHIMA Keiko, FUTASE Atsuko, MORI Fumiaki, SAWABE Motoji, HAGIWARA Nobuhisa
発行年月 2018/05
概要 Background: Adhesion molecules have essential roles for the development of atherosclerosis. We examined whether PSGL-1 expressing CD4 T cells in acute coronary syndrome (ACS) contribute to plaque instability.

Methods and Results: CD4 T cells were isolated from the peripheral blood (PB) of 36 ACS patients (AMI=23, UAP=13) and 24 healthy controls (NC). CD4 T cells from ACS strongly expressed PSGL-1 and integrin β2 (P<0.05 and P<0.05, respectively), but not L-selectin and integrin αM by FACS. We investigated the thrombus-aspirating device samples (n=22) and CD4 T cells derived from both the coronary artery (CA) and PB from the same ACS patients. We confirmed culprit lesion contained abundant PSGL-1+CD4+ T cells (P<0.001), but not integrin β2+CD4+ T cells by FACS. In addition, immunohistochemistry revealed that many PSGL-1+CD4+ T cells were in the plaques and thrombus from the culprit lesion. To investigate whether PSGL-1+CD4+ T cells from ACS could bind to P-selectin or E-selectin, we analyzed PSGL-1+CD4+ T cells by selectin binding assay. PSGL-1+CD4+ T cells strongly bound to both P-selectin and E-selectin after TCR triggering. Furthermore, apoptosis assay of endothelial cells (EC) showed that PSGL-1+CD4+ T cells from CA strongly induced EC apoptosis compared to those from PB (P<0.01). In addition, EC apoptosis correlated with the expression of PSGL-1 (R=0.788, P<0.03), and was inhibited by anti-PSGL-1 Ab (P<0.05). Finally, we investigated the mechanism of PSGL-1+CD4+ T cells induced EC apoptosis. EC co-cultured with PSGL-1+CD4+ T cells from ACS strongly expressed PARP by immunohistochemistry and active caspase-3 by FACS.

Conclusions: From these results, we demonstrated that PSGL-1 expressing CD4 T cells participate directly in the acceleration of plaque instability in ACS.
DOI doi:10.1253/circj.CJ-17-1270