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

Tolerance induction to transplantation-associated carbohydrate antigens, such as blood group A or B and the alpha-gal epitope (Gal(alpha)1-3Gal(beta)1-4GlcNAc-R), is of clinical significance. This study demonstrates tolerance induction to the alpha-gal epitope in the experimental animal model of alpha1,3galactosyltransferanse knockout mice (KO mice) lacking alpha-gal epitopes by administering syngeneic lymphocytes expressing alpha-gal epitopes. Repeated immunization of control KO mice with pig kidney membranes (PKM) expressing many alpha-gal epitopes induces an extensive anti-Gal antibody response against this epitope. In contrast, KO mice that received as few as 2 x 10(6) 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.