Scherer, Marcus N. and Graeb, Christian and Tange, Stefan and Dyson, Chrissie and Jauch, Karl-Walter and Geissler, Edward K. (2000) Immunologic considerations for therapeutic strategies utilizing allogeneic hepatocytes: Hepatocyte-expressed membrane-bound major histocompatibility complex class I antigen sensitizes while soluble antigen suppresses the immune response in rats. HEPATOLOGY, 32 (5). pp. 999-1007. ISSN 0270-9139, 1527-3350
Full text not available from this repository. (Request a copy)Abstract
Understanding the immunologic effects of hepatocytes is critical because of the potential to use these cells for bioartificial livers, as a vehicle for gene transfer, and as a means to induce donor-specific immunosuppression in organ transplantation, However, this understanding is complicated by the fact that hepatocytes express membrane-bound and soluble forms of major histocompatibility complex (MHC) class I antigen, each with the potential to induce different immune responses. In the present study we first determined the immunologic effect of normal donor-derived hepatocytes in a rat heart transplant model. We then used ex vivo hepatocyte gene transfer to examine the immunologic effects of different forms of hepatocyte-expressed MHC class I antigen, Results showed that intrasplenic injection of purified, donor-strain-specific hepatocytes into recipients primes alloimmunity, as evidenced by acceleration of heart allograft rejection. Interestingly, injection of autologous hepatocytes transfected ex vivo with DNA encoding only membrane-bound donor MHC class I antigen (RT1.A(a)) also accelerated allograft rejection. However, hepatocytes transfected to express only secreted donor MHC antigen prolonged transplant survival. Limiting-dilution analysis of lymphocytes from animals treated with hepatocytes producing only secreted alloantigen showed an antigen-specific reduction in cytotoxic T lymphocyte (CTL) and helper T lymphocyte (HTL) precursors. Further analysis of CTL populations by flow cytometry revealed a relatively high percentage of nonviable cells, implying that soluble antigen promotes allospecific CTL death. In summary, this study suggests that hepatocyte-expressed MHC class I molecules have opposing immunologic effects, with the membrane-bound antigen inducing immunologic sensitization, and the soluble antigen promoting donor-specific immunosuppression.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HLA CLASS-I; PORTAL VENOUS TOLERANCE; GENE-THERAPY; LIVER-TRANSPLANTATION; T-CELLS; ALLOGRAFT; MODEL; MOLECULES; LYMPHOCYTES; INHIBITION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Mar 2022 17:12 |
| Last Modified: | 16 Mar 2022 17:12 |
| URI: | https://pred.uni-regensburg.de/id/eprint/42086 |
Actions (login required)
 |
View Item |
