Objective       To investigate the effects of cytotoxic T lymphocyte associated antigen 4 immuno-globulin (CTLA4Ig) and cluster of differentiation 40 ligand immunoglobulin (CD40LIg) modified bone marrow mesenchymal stem cells (MSCs) on rejection of rat islet xenografts.       Methods       The islet xenografts model of SD-Wistar rat was established with islet cells of SD rats transplant under left kidney capsule of diabetic Wistar rats. MSCs infected with recombinant adenoviruses containing CTLA4Ig and CD40LIg gene were applied in treatment. Forty-five successfully modeling diabetic rats were randomly divided into three groups with 15 rats in each group: only islet cells were transplanted to rats in control group (A); islet cells and MSCs were transplanted to rats in MSCs group (B); and islet cells and MSCs transfected with CTLA4Ig and CD40LIg gene were transplanted to rats in transfected MSCs group (C). Survival of rats

blood glucose and morphological changes of grafts were observed after islet transplantation. Expressions of CTLA4Ig

CD40LIg and insulin were detected by immunohistochemical staining and cytokines changes were quantified by ELISA.       Results      ①The blood glucose of transplant rats decreased to normal level on day 2 post-transplantation. The average level of blood glucose of group A

group B and group C increased on day 8

21 and 49 post-transplantation

respectively. ②The grafts of the group A

B and C survived for (10.2±2.1)

(23.5±6.8) and (52.1±7.3) days

respectively. There were significant differences among group A

B and C (P0.05). The survival time of transplant rats were (21.3±5.3)

(49.7±8.5) and (95.8±13.8) days in group A

B and C

respectively. The survival time of transplant rats among each group was the same as that of grafts (P0.05). ③In group A

serum levels of IL-2 and TNF-α increased dramatically and serum levels of IL-4 and IL-10 decreased significantly within 7 days post-transplantation compared with those before transplantation (P0.01). Serum levels of IL-4 and IL-10 in group B and C increased significantly post-transplantation compared with those before transplantation. ④Hematoxylin-eosin staining of grafts showed in group B and C

bolus of islets under kidney capsule with no lymphocytes infiltration and immunohistochemical staining of grafts showed expression of insulin protein at islets in group B and C. These grafts positively stained for CTLA4Ig and CD40LIg in group C.       Conclusion      CTLA4Ig and CD40LIg modified MSCs can inhibit the rejection of rat islet xenografts

and the effect are superior to MSCs alone.