Tolerance induction to a mammalian blood group–like carbohydrate antigen by syngeneic lymphocytes expressing the antigen

Abstract
Tolerance induction to transplantation-associated carbohydrate antigens, such as blood group A or B and the α-gal epitope (Galα1-3Galβ1-4GlcNAc-R), is of clinical significance. This study demonstrates tolerance induction to the α-gal epitope in the experimental animal model of α1,3galactosyltransferanse knockout mice (KO mice) lacking α-gal epitopes by administering syngeneic lymphocytes expressing α-gal epitopes. Repeated immunization of control KO mice with pig kidney membranes (PKM) expressing many α-gal epitopes induces an extensive anti-Gal antibody response against this epitope. In contrast, KO mice that received as few as 2 × 106 wild-type (WT) lymphocytes were tolerized and failed to produce anti-Gal following PKM immunizations. Accordingly, control mice producing anti-Gal rapidly rejected transplanted WT hearts, whereas tolerized mice did not reject WT hearts. These findings suggest that autologous blood lymphocytes processed to express a carbohydrate antigen may induce a similar tolerance to such an antigen upon administration into humans.