[Preoperative inoculation of CTLA4Ig combined with allogeneic dendritic cells prolongs rat renal allograft survival in a donor-specific fashion].
Donor dendritic cells (DCs) within allografts initiate the induction of allospecific T cell response, while abortive alloantigen presentation by DCs may induce allospecific unresponsiveness. It thus seems important to determine if preoperative transfusion of donor DCs in conjunction with CTLA4Ig would prolong graft survival, in a donor-specific manner. Rats treated with donor DCs (2 x 10(6)/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 accelerated rejection (5.6 +/- 1.7 days). When DCs and CTLA4Ig (500 mg/rat i.p. on days -9, -7, and -5) were concomitantly inoculated, allograft survival was significantly prolonged (> 38.8 +/- 38.3 days); preoperative inoculation of CTLA4Ig 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 into the transplanted kidneys in the long-term survivors. The serum cytokine profiles were almost identical between the experimental groups of long-term survivors; that is the relative predominance of IL-4 and IL-10 in the early and late phases of the graft enhancement, respectively. The above collective evidence suggests that as preoperative treatment with donor DCs in combination with CTLA4Ig prolongs graft survival, and supports the notion that abortive alloantigen presentation by DCs conveys allospecific unresponsiveness.
Harada
H
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Department of Urology, Hokkaido University School of Medicine, Sapporo, Japan.
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000008:administration & dosage*; D060908:CTLA-4 Antigen; D003713:Dendritic Cells / Q000637:transplantation*; D004195:Disease Models, Animal; D006085:Graft Survival; D018796:Immunoconjugates; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000276:immunology*; D011300:Preoperative Care; D051381:Rats; D011919:Rats, Inbred Strains; D014019:Tissue Donors; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556708:Ctla4 protein, rat; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D000069594:Abatacept