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ラット同種腎移植における術前ドナー樹状細胞およびCTLA4Ig投与による移植片生着延長効果

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Title: ラット同種腎移植における術前ドナー樹状細胞およびCTLA4Ig投与による移植片生着延長効果
Other Titles: Preoperative Inoculation of CTLA4Ig Combined with Allogeneic Dendritic Cells Prolongs Rat Renal Allografts in a Donor-Specific Fashion
Authors: 原田, 浩1 Browse this author
Authors(alt): Harada, Hiroshi1
Keywords: Renal transplantation
Donor specific tolerance
Dendritic cell
Costimulatory signal
CTLA4Ig
Issue Date: 25-Mar-1999
Abstract: Donor dendritic cells (DCs) within allografts initiate the induction of an allospecific T cell response, while an abortive alloantigen presentation by DCs may induce allospecific unresponsiveness. It thus seems important to determine if a preoperative transfusion of donor DCs in conjunction with CTLA4Ig would prolong graft survival, in a donorspecific manner. Rats treated with donor DCs (2x1O6/rat i.v.) on the preoperative day 9 rejected allografts in an accelerated manner (5.0±2.2 vs. 8.2±1.6 days in the control group). Preoperative transfusion of DCs pulsed with CTLA4Ig, a procedure which suppresses an allogeneic mixed lymphocyte reaction (MLR), also provoked an accelerated rejection (5.6±1.7 days). When DCs and CTLA4Ig (500mg/rat i.p. on days -9, -7, and -5) were concomitantly inoculated, allograft survival was significantly prolonged (>38.8±38.3 days); a preoperative CTLA4Ig inoculation alone failed to do so (7.5±1.2 days). Postoperative CTLA4Ig alone prolonged graft survival (>68.1±39.0 days). Long-term graft survivors tolerated skin grafts from the donor but not those from a third party. There were no cellular infiltrates within transplanted kidneys in the long-term survivors. The serum cytokine profiles were almost identical between the experimental groups with long-term survivors: the relative predominance of IL-4 and IL-10 in the early and late phases in the graft enhancement, respectively. The collective evidence suggests that as preoperative treatment of donor DCs in combination with CTLA4Ig prolongs graft survival, and the notion that an abortive alloantigen presentation by DCs conveys allospecific unresponsiveness is given support.
Description: running title: 樹状細胞,CTLA4Igによる移植片生着延長
Conffering University: 北海道大学
Degree Report Number: 甲第4684号
Degree Level: 博士
Degree Discipline: 医学
Type: theses (doctoral)
URI: http://hdl.handle.net/2115/51585
Appears in Collections:学位論文 (Theses) > 博士 (医学)

Submitter: 原田 浩

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