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   非常勤講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	High PD-L1/CD86 ratio on plasmacytoid dendritic cells correlates with elevated T-regulatory cells in liver transplant tolerance.
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	85(3),pp.369-77
著者・共著者	Tokita Daisuke, Mazariegos George V, Zahorchak Alan F, Chien Nydia, Abe Masanori, Raimondi Giorgio, Thomson Angus W
担当区分	筆頭著者
発行年月	2008/02
概要	BACKGROUND:Both dendritic cells (DC) and T-regulatory cells (Treg) have been implicated in regulation of alloimmune responses and transplant tolerance.METHODS:We analyzed B7 coregulatory molecule expression on circulating DC subset precursors, together with CD4+CD25(hi) Foxp3+ Treg by rare event, flow cytometric analysis in operationally tolerant pediatric liver transplant recipients (TOL), those undergoing prospective immunosuppressive drug weaning (PW) or maintenance immunosuppression (MI), and normal healthy individuals (controls).RESULTS:Use of DC subset-specific monoclonal antibodies confirmed elevated precursor plasmacytoid DC/myeloid DC ratios in TOL and PW compared with MI. In addition, Treg frequencies were higher in TOL than in PW and MI, but not controls. While there was no difference in levels of costimulatory and coinhibitory molecules on precursor myeloid DC between the groups, the programmed death ligand-1 (PD-L1=B7-H1):CD86 (B7-2) ratio on precursor plasmacytoid DC was significantly higher in TOL than MI and correlated with the Treg frequency. There was no relation between prednisone or tacrolimus dose or tacrolimus trough level and either the PD-L1/CD86 ratio on plasmacytoid DC or the Treg frequency. Moreover, clinically relevant concentrations of dexamethasone or tacrolimus did not affect these values in short-term culture.CONCLUSION:These novel findings suggest a possible functional relationship between the enhanced incidence of precursor plasmacytoid DC, their comparatively high relative expression of the coinhibitory molecule PD-L1, and the elevated frequency of Treg in operational liver transplant tolerance.
DOI	10.1097/TP.0b013e3181612ded
PMID	18301333