Graeb, Christian and Justl, Martin and Scherer, Marcus N. and Andrassy, Joachim and Frank, Erika and Zuelke, Carl and Jauch, Karl-Walter and Geissler, Edward K. (2002) Use of an adenoviral vector to express soluble donor-major histocompatibility complex molecules capable of suppressing the immune response in rat transplant recipients. HUMAN IMMUNOLOGY, 63 (10): PII S0198-. pp. 844-852. ISSN 0198-8859
Full text not available from this repository.Abstract
There is an accumulating body of evidence indicating that soluble major histocompatibility complex (sMHC) molecules have donor-specific immunosuppressive properties. One classic, but still unproven, theory is that production of sMHC by liver transplants induces a potent immunosuppressive effect. To mimic this possible effect, we have developed a replication deficient adenovirus (Ad-RQ) to express high levels of donor sMHC class I molecules (sRT1.A(a)) in the liver. Ad-RQ produced sRT1.A(a) was measured by enzyme-linked immunosorbant assay (ELISA) after in vitro infection of Lewis (RT1(t)) hepatocytes, and in vivo following intravenous virus injection into Lewis rats. Results indicated high sRT1.A(a) expression in Lewis hepatocyte cultures and, in vivo, high expression was also demonstrated and maintained for at least I week. A strong immunosuppressive potential of sMHC in vivo was revealed by prolongation of cardiac (ACI, RT1(a)) heart allograft Survival in high-responder Lewis rat recipients treated with Ad-RQ alone. Furthermore, limiting dilution cytotoxic T-lymphocyte precursor (CTLp) analysis of lymphocytes from Ad-RQ-treated Lewis recipients receiving an ACI heart transplant indicated a marked decrease in antidonor CTLp frequency. In conclusion, our results demonstrate that viral vectors can be used effectively to express high levels of sMHC molecules, and their immunosuppressive effect, without concurrent immunosuppression, is sufficiently potent to prolong heart transplant Survival. (C) American Society for Histocompatibility and Immunogenetics, 2002, Published by Elsevier Science Inc.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CLASS-I ANTIGEN; GREEN FLUORESCENT PROTEIN; CYTOTOXIC T-LYMPHOCYTE; LIVER-TRANSPLANTATION; ORGAN-TRANSPLANTATION; GENE-THERAPY; IMMUNOSUPPRESSION; HEPATOCYTES; TOLERANCE; REJECTION; adenoviral vectors; CTL; heart transplantation; soluble MHC class I |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 Oct 2021 08:47 |
| Last Modified: | 04 Oct 2021 08:47 |
| URI: | https://pred.uni-regensburg.de/id/eprint/39826 |
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