Geissler, Edward K. and Graeb, Christian and Tange, Stefan and Guba, Marcus and Jauch, Karl-Walter and Scherer, Marcus N. (2000) Effective use of donor MHC class I gene therapy in organ transplantation: Prevention of antibody-mediated hyperacute heart allograft rejection in highly sensitized rat recipients. HUMAN GENE THERAPY, 11 (3). pp. 459-469. ISSN 1043-0342, 1557-7422
Full text not available from this repository. (Request a copy)Abstract
Immunologically sensitized recipients present one of the most critical problems in clinical organ transplantation today, since preformed antibodies rapidly destroy donor tissue expressing specific MHC class I antigens (Ag), Therefore, sensitized patients are either unable to receive a compatible organ, or experience a prolonged waiting period. In this study we examined the effectiveness of donor MHC class I gene therapy in preventing hyperacute rejection (HR) of rat heart allografts in passively sensitized recipients. Our gene therapy strategy to address this problem is based on the phenomenon that liver transplants, which resist antibody-mediated HR, produce soluble MHC class I Ag capable of neutralizing:preformed antibodies and suppressing the immune response. To mimic this "liver effect," we used liposomes to transfect cultured recipient (Lewis-RT1.A(1)) hepatocytes with plasmid DNA encoding the soluble: donor MHC class I Ag, RT1.A(a), Control or RT1.A(a)-transfected hepatocytes were implanted intrasplenically into Lewis recipients 1 day prior to heterotopic ACI (RT1.A(a)) heart transplantation and injection of 6 ml of anti-ACI hyperimmune serum (HIS), Results showed that nearly all recipients receiving ACI-specific HIS and control hepatocytes experienced HR, while none of the recipients receiving HIS and hepatocytes expressing soluble RT1.A(a) developed HR, Furthermore, active immunosuppression by soluble RT1.A(a) was evidenced by prolongation of allograft survival, compared with controls not receiving HIS. In summary, soluble donor-MHC class I Ag gene therapy can prevent antibody-mediated destruction associated with HR, Future development of a similar strategy in humans may significantly improve the results of clinical organ transplantation in immunologically sensitized recipients.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HLA CLASS-I; MAJOR HISTOCOMPATIBILITY COMPLEX; PORTAL-VEIN; LIVER; ANTIGEN; HEPATOCYTES; PROTEIN; SUPPRESSION; RESPONSES; MOLECULES; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Jun 2022 06:36 |
| Last Modified: | 07 Jun 2022 06:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/42826 |
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