Title: Costimulatory blockade with anti-inducible costimulator antibody in conjunction with CTLA4Ig on prevention of islet allograft rejection
Abstract: Objective To study the effects of costimulatory blockade with anti-inducible costimula- tor antibody in conjunction with CTLA4Ig on preventiun of islet allograft rejection.Methods Experimental animals were divided into 4 groups in random,10 rats in each group:The CTLA4Ig and ICOS mAb-treated group:intraperitoneal injection of CTLA4Ig 50μg/kg on day 0,2,4 and ICOS mAb 100μg/kg on day 1,3 and 5 after islet transplantation;The ICOS mAb-treated group:intraperitoneal injection of ICOS mAb 100μg/kg on day 1,3 and 5 after islet transplantation;The CTLA4Ig-treated group:intraperitoneal injection of CTLA4Ig 50μg/kg on day 0,2 and 4 after islet transplantation;Control group:simple islet transplantation, not subject to CTLA4Ig and ICOS mAb.HE stain for kidney was used to evaluate the histology,and immuno- histochemical stain of insubn-Ab used to determine the expression of insulin.The expression of CD4~+ and CD8~+ T cells was detected by flow cytometry.The expression of IL-2 and IL-10 mRNA was detected by RT- PCR.Results The mean survival time in CTLA4Ig and ICOS mAb-treated group was(31.00±6.57) days,which was significanntly different from that in other three groups(P0.05).The expression level of IL-2 mRNA in CTLA4Ig and ICOS mAb-treated group was(44.23±6.24),which was obviously different from other three groups(P0.05),but there was no significant difference in the expression level of IL-10 mRNA between among the groups(P0.05).The number of CD4~+ and CD8~+ T cells in CTLA4Ig and ICOS mAb-treated group was(13.73±0.49)% and(14.56±0.31)% respectively,showing no obvious up-regulation on the day 21 after transplantation.Uner light microscopy,the morphology of islets was close to the normal.Conclusion The blockade of costimulatory signals with ICOS mAb in conjunction with CT- LA4Ig has a favorable effect to restrain the rejection of islet transplantation.
Publication Year: 2007
Publication Date: 2007-01-01
Language: en
Type: article
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