Cutting Edge: Pig Islet Xenografts Are Susceptible to “Anti-Pig” But Not Galα(1,3)Gal Antibody Plus Complement in Gal o/o Mice

Abstract

Hyperacute rejection due to Galα(1,3)Gal (Gal) Ab plus complement (C′) is a major problem in xenografting vascularized organs from pigs to primates, but the fate of neovascularized xeno islets is unclear. Nonendocrine islet cells are Gal+, and there is a large rise in Gal Abs after transplantation, but graft remnants persist for some days in monkeys and humans. To define the role of αGal Ab plus C′ in porcine islet graft rejection, cultured porcine fetal islets were grafted to mice lacking the α(1,3)galactosyltransferase gene. Anti-Gal Ab plus C′ did not cause islet damage or rejection in mice lacking the α(1,3)galactosyltransferase gene, even when additional Ab plus C′ was given; in addition, hyperimmune mice (titer >1/20,000) did not reject pig islets, showing that islets are resistant to Gal Ab plus C′. However, islets can be destroyed by polyclonal mouse anti-pig Abs. Thus, the focus of islet xenografting should not be on Gal Ab plus C′.