Jager, Mark D. and Liu, Han Y. and Timrott, Kai F. and Popp, Felix C. and Stoeltzing, Oliver and Lang, Sven A. and Piso, Pompiliu and Geissler, Edward K. and Schlitt, Hans J. and Dahlke, Marc H. (2007) Sirolimus promotes tolerance for donor and recipient antigens after MHC class II disparate bone marrow transplantation in rats. EXPERIMENTAL HEMATOLOGY, 35 (1). pp. 164-170. ISSN 0301-472X,
Full text not available from this repository. (Request a copy)Abstract
Objective. Mixed chimerism after allogeneic bone marrow transplantation (BMT) promotes immunologic tolerance. Graft-vs-host disease (GvHD) can occur when immunosuppressive control of the graft fails. Here we evaluate the influence of concurrent immunosuppression after irradiation-based induction therapy on development of tolerance and GvHD. Methods. Conditioning was performed by different doses of total body irradiation (TBI) in a major histocompatibility complex (MHC) class II disparate rat BMT model. Animals received subsequent immunosuppression with either cyclosporine A (CsA) or sirolimus. Nonresponsiveness toward donor and recipient antigens was demonstrated by development of mixed chimerism and/or GvHD. Results. Administration of 10 Gy of TBI prior to BMT alone was associated with severe GvHD. Induction therapy with 8 Gy of TBI alone led to graft rejection in the long-term. Two weeks of immunosuppression with CsA after 8 Gy of TBI resulted in transient chimerism, but was finally associated with a combination of fatal GvHD and graft rejection. Six gray of TBI with CsA treatment for 14 or 28 days caused only mild GvHD, but did not lead to stable chimerism. In contrast, treatment with sirolimus was associated with stable chimerism after 8 Gy of TBI (14-day course) and 6 Gy of TBI (28-day course) accompanied by a low incidence of GvHD. Conclusions. In contrast to CsA, sirolimus facilitates development of tolerance after MHC class II disparate BMT and irradiation-based conditioning, with a low risk of GvHD. Therefore, sirolimus has promising characteristics for inclusion in immunosuppressive protocols. (c) 2007 International Society for Experimental Hematology. Published by Elsevier Inc.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VERSUS-HOST-DISEASE; CYCLOSPORINE-A; T-CELLS; RAPAMYCIN; GRAFT; CHIMERISM; MICE; IMMUNOTHERAPY; REGENERATION; LYMPHOCYTES; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Jan 2021 07:37 |
| Last Modified: | 12 Jan 2021 07:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/33413 |
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