Costimulatory blockade with anti-inducible costimulator antibody in combination with CTLA4Ig on prevention of islet allograft rejection / 中华器官移植杂志

ABSTRACT

Objective To study the effects of costimulatory blockade with anti-inducible costim- ulator antibody(ICOS mAb)in combination with CTLA4Ig on prevention of islet allograft rejection. Methods Experimental animals were randomly divided into 4 groups(10 rats in each group).CT- LA4Ig + ICOS mAb group(group A)intraperitoneal injection of CTLA4Ig on day 0,2,4 and ICOS mAb on day 1,3,5 after islet transplantation;ICOSmAb group(group B)intraperitoneal injection of ICOS mAb on day 1,3,5 after islet transplantation;CTLA4Ig group(group C)intraperitoneal injection of CTLA4Ig on day 0,2,4 after islet transplantation;control group(group D)simple islet transplantation.The islet allograft survival and pathological changes in the transplanted islets after transplantation were observed.By using RT-PCR,the expression of IL-2 and IL-10 mRNA in the transplanted islets was detected.The expression of CD4~+ and CD8~+ T cell was detected by flow cy- tometry.Results In group A,the survival time was obviously prolonged as compared with other three groups and the transplanted islets were near normal under a light microscope.As compared with other three groups,the expression of IL-2 mRNA was significantly decreased in group A(P0.05).The expression of CD4~+ and CD8~+ T cell was not obviously up-regulated on the day 21 after transplantation.Conclusion The blockade of costimulatory signals with ICOS mAb in combination with CTLA4Ig has a favorable effects to restrain the rejection of islet transplantation.