Objective: To investigate the effect of cytotoxic T lymphocyte-associated antigen 4 immunoglobulin (CTLA4-Ig) gene transfer on rejection of rat islet xenografts.
Methods: Human islets were infected with the recombinant adenoviruses containing CTLA4-Ig gene, and the transduced islets were transplanted under the left kidney capsule of diabetic rats to establish rat models bearing human-rat islet xenografts. The blood sugar of the rats receiving the transplantation was measured and the xenografts and host survival were observed after transplantation. The morphological changes of grafts were examined, in which the expression of CTLA4-Ig and insulin were also detected by immunohistochemical staining and the cytokines were quantified using enzyme-linked immunosorbent assay (ELISA).
Results: The blood glucose of the rats bearing the grafts decreased to the normal level on day 2 after transplantation. The average blood glucose level of the CTLA4-Ig gene transfected group and the control group increased on day 25 and 8 post-transplantation, respectively. The grafts of the transfected group survived for an average of 28-/+6 days, significantly longer than that in the control group (10-/+2 days, t=10.52, P<0.01), and the host survival were 48-/+8 and 21-/+6 days in the two groups, showing also significant difference between them (t=12.23, P<0.01). In the control rats, serum IL-2 and TNF-alpha concentration drastically increased within 7 days after transplantation to levels significantly higher than that before transplantation (P<0.01), but in the transfected group, the levels were decreased compared with the preoperative levels. In the transfected grafts, positive staining for CTLA4-Ig and insulin were detected.
Conclusion: CTLA4-Ig gene transfer may lower the rejection of rat islet xenografts and prolong the survival time of both the grafts and hosts.