トキタ ダイスケ   TOKITA Daisuke
  時田 大輔
   所属   医学部 医学科(東京女子医科大学病院)
   職種   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 Infusion of stably immature monocyte-derived dendritic cells plus CTLA4Ig modulates alloimmune reactivity in rhesus macaques.
掲載誌名 正式名:Transplantation
略  称:Transplantation
ISSNコード:00411337/00411337
掲載区分国外
巻・号・頁 84(2),pp.196-206
著者・共著者 Zahorchak Alan F, Kean Leslie S, Tokita Daisuke, Turnquist Heth R, Abe Masanori, Finke Jennifer, Hamby Kelly, Rigby Mark R, Larsen Christian P, Thomson Angus W
発行年月 2007/07
概要 BACKGROUND:Immature dendritic cells (DC) can promote long-term transplant survival in rodents. We assessed the impact of stably immature, donor-derived DC on alloimmune reactivity in rhesus macaques.METHODS:CD14 monocytes isolated from leukapheresis products of Macacca mulatta were cultured in granulocyte-macrophage colony stimulating factor plus interleukin (IL)-4+/-vitamin (vit) D3, and IL-10. Major histocompatibility complex class II and cosignaling molecule expression was determined on CD11c cells by flow cytometry. T-cell allostimulatory capacity of the DC, including DC exposed to proinflammatory cytokines, was determined in mixed leukocyte reaction. To test their influence in vivo, purified DC were infused intravenously into allogeneic recipients, either alone or followed by CTLA4Ig, 24 hr later. Proliferative responses of recipient CFSE-labeled T cells to donor or third party DC, cytokine production by stimulated T cells, and circulating alloantibody levels were determined by flow cytometry, up to 100 days postinfusion.RESULTS:VitD3/IL-10-conditioned, monocyte-derived DC were resistant to maturation and failed to induce allogeneic T cell proliferation in vitro. After their infusion, an increase in anti-donor and anti-third party T-cell reactivity was observed, that subsequently subsided to fall significantly below pretreatment levels (by day 56) only in animals also given CTLA4Ig. No increase in circulating immunoglobulin (Ig) M or IgG anti-donor alloantibody titers compared with pretreatment values was detected. With DC+CTLA4Ig infusion, alloreactive IL-10-producing T cells were prevalent in the circulation after day 28.CONCLUSIONS:Maturation-resistant rhesus DC infusion is well-tolerated. DC+CTLA4Ig infusion modulates allogeneic T-cell responses and results in hyporesponsiveness to donor and third party alloantigens.
DOI 10.1097/01.tp.0000268582.21168.f6
PMID 17667811