CUTTING EDGE - PIG ISLET XENOGRAFTS ARE SUSCEPTIBLE TO ANTI-PIG BUT NOT GAL-ALPHA(1,3)GAL ANTIBODY PLUS COMPLEMENT IN GAL O O MICE/

Hyperacute rejection due to Gal alpha(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 alpha Gal Ab plus C' in por cine islet graft rejection, cultured porcine fetal islets were grafted to mice lacking the alpha(1,3)galactosyltransferase gene. Anti-Gal Ab plus C' did not cause islet damage or rejection in mice lacking the a lpha(1,3)galactosyltransferase gene, even when additional Ab plus C' w as given; in addition, hyperimmune mice (titer >1/ 20,000) did not rej ect pig islets, showing that islets are resistant to Gal Ab plus C'. H owever, islets can be destroyed by polyclonal mouse anti-pig Abs, Thus , the focus of islet xenografting should not be on Gal Ab plus C'.