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Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-07-2151.

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Submitted July 18, 2002
Accepted October 21, 2002

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

Haruko Ogawa, Deng-Ping Yin, Jikun Shen, and Uri Galili*

Department of Cardivascular-Thoracic Surgery, Rush University, Chicago, IL, USA
Department of Surgery, Rush University, Chicago, IL, USA
Department of Cardivascular-Thoracic Surgery, Rush University, Chicago, IL, USA; Department of Immunology and Microbiology, Rush University, Chicago, IL, USA

* Corresponding author; email: uri_galili{at}rush.edu.

Tolerance induction to transplantation associated carbohydrate antigens, such as blood group A or B and the {alpha}-gal epitope (Gal{alpha}1-3Galß1-4GlcNAc-R), is of clinical significance. This study demonstrates tolerance induction to the {alpha}-gal epitope in the experimental animal model of {alpha} 1,3galactosyltransferanse knockout mice (KO mice lacking a-gal epitopes), by administering syngeneic lymphocytes expressing {alpha}-gal epitopes. Repeated immunization of control KO mice with pig kidney membranes (PKM), expressing many a-gal epitopes, induces an extensive anti-Gal antibody response against this epitope. In contrast, KO mice that received as few as 2x106 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 antigen upon administration into humans.


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