Failure of transplantation tolerance induction by autologous regulatory T cells in the pig‐to‐non‐human primate islet xenotransplantation model

• DOI: 10.1111/xen.12246
• Publication Date: 2016-07-08T04:46:49Z
• Authors: Jun‐Seop Shin; Byoung‐Hoon Min; Jong‐Min Kim; Jung‐Sik Kim; Il Hee Yoon; Hyun Je Kim; Yong‐Hee Kim; Jae Yool Jang; Hee Jung Kang; Dong‐Gyun Lim; Jongwon Ha; Sang‐Joon Kim; Chung‐Gyu Park
• Keywords: Xenotransplantation; Allotransplantation; Immunosuppression; Sirolimus; Thymoglobulin; Miniature swine

Abstract Background Islet allotransplantation is a promising way to treat some type 1 diabetic (T1D) patients with frequent hypoglycemic unawareness, and islet xenotransplantation emerging overcome the problem of donor organ shortage. Our recent study showing reproducible long‐term survival porcine islets in non‐human primates ( NHP s) allows us examine whether autologous regulatory T‐cell (Treg) infusion at peri‐transplantation period would induce transplantation tolerance setting. Methods Two rhesus monkeys were transplanted from wild‐type adult Seoul National University SNU ) miniature pigs immunosuppression by anti‐thymoglobulin ATG ), cobra venom factor, anti‐ CD 154 monoclonal antibody mA b), sirolimus. 4 + 25 high 127 low T cells recipients isolated, ex vivo expanded, infused period. Blood glucose C‐peptide measured up 1000 days. Maintenance immunosuppressants including 40‐ blockade deliberately discontinued confirm was induced adoptively transferred Tregs. Results After pig via portal vein, blood levels became normalized maintained over 6 months while immunosuppressive maintenance However, engrafted fully rejected activated immune cells, particularly when stopped, failure induction Conclusions Taken together, Tregs failed pig‐to‐