These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: 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.
    Author: Geissler EK, Graeb C, Tange S, Guba M, Jauch KW, Scherer MN.
    Journal: Hum Gene Ther; 2000 Feb 10; 11(3):459-69. PubMed ID: 10697120.
    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.Al) hepatocytes with plasmid DNA encoding the soluble donor MHC class I Ag, RT1.Aa. Control or RT1.Aa-transfected hepatocytes were implanted intrasplenically into Lewis recipients 1 day prior to heterotopic ACI (RT1.Aa) 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.Aa developed HR. Furthermore, active immunosuppression by soluble RT1.Aa 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.
    [Abstract] [Full Text] [Related] [New Search]