Title: Inhibition of acute allograft rejection in mouse pancreas allograft models by combined treatment with PD-L1.Ig and 1,25-dihydroxyvitamin D3
Abstract: Objective To investigate the effects of PD-L1.Ig combined with 1,25(OH)_2 D_3 on the acute rejection of pancreatic allograft in the rat model,and the synergic effects of them in prolonging survival time of vascularized pancreatic allograft.Methods Pancreatic aUograft from F344 rats was trans- planted to Lewis recipients.Experimental animals were randomly divided into 4 groups,12 rats for each: group A(negative control);group B(intraperitoneal injection of PD-L1.Ig on day 0,2 and 4 after pan- creas transplantation);group C(allograft recipients receiving daily intraperitoneal injection of 1,25-di- hydmxyvitamin D3);group D(allotransplantation and a combination of intraperitoneal PD-L1.Ig and 1, 25-dihydroxyvitamin D3).The blood glucose in the recipients,the pathological changes of the allografts and the survival of pancreatic allografts were observed.The peripheral blood,spleens and grafts were har- vested from the recipients for determination of CD3~+CD8~+T cells,CD4+T cells and CD4~+ CD25~+ T by flow cytometry.After transplantation,the level of graft interleukin-2,4,10,12 in the recipients was deter- mined by ELISA kit analysis.The mixed lymphocyte reaction(MLR)of the donors with the recipient spleen cells was performed.Results Comparing with group A,allografts survival time was not significantly prolonged in group B(P0.05),which in groups C and D,the recipient survival time was significantly prolonged and blood glucose level significantly reduced.The survival time of pancreas grafts was longest in group D.The number of CD3~+ CD8~+ T cells and CD4~+ T cells was decreased in groups B,C and D as com- pared with group A(P0.01).Concentration of Th1-type cytokine in allograft decreased markedly,Th2 cytokine increased significantly.The donor-specific MLR was suppressed in spleen cell cultures.Conclu- sion Combined use of PD-L1.Ig and 1,25-dihydroxyvitamin D3 may suppress the cell-mediated immune responses and pancreas allograft rejection effectively and promote further prolongation of the survival of pancreas allografts.
Publication Year: 2007
Publication Date: 2007-01-01
Language: en
Type: article
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