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.
Ogawa
Haruko
H
Department of Cardiovascular-Thoracic Surgery, Rush University, Chicago, IL 60612, USA.
Yin
Deng-Ping
DP
Shen
Jikun
J
Galili
Uri
U
D000818:Animals; D000941:Antigens / Q000235:genetics* / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology; D005700:Galactosyltransferases / Q000172:deficiency; D006084:Graft Rejection / Q000276:immunology; D016027:Heart Transplantation; D007108:Immune Tolerance; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007668:Kidney / Q000648:ultrastructure; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013552:Swine; D016042:Transplantation, Heterotopic; D014312:Trisaccharides / Q000172:deficiency / Q000276:immunology*
D000941:Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D014312:Trisaccharides; C076569:alpha-galactosyl epitope; D005700:Galactosyltransferases; C047006:N-acetyllactosaminide alpha-1,3-galactosyltransferase