open access

https://doi.org/10.11501/3151367

https://hdl.handle.net/2115/51585

Preoperative Inoculation of CTLA4Ig Combined with Allogeneic Dendritic Cells Prolongs Rat Renal Allografts in a Donor-Specific Fashion

日本語

CTLA4Ig

1999-03-25

Hokkaido University

running title: 樹状細胞，CTLA4Igによる移植片生着延長

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.

1999-03-25

甲第4684号

博士(医学)

博士論文

Version of Record