Kuehne, Louisa and Jung, Bettina and Poth, Helen and Schuster, Antonia and Wurm, Simone and Ruemmele, Petra and Banas, Bernhard and Bergler, Tobias (2017) Renal allograft rejection, lymphocyte infiltration, and de novo donor-specific antibodies in a novel model of non-adherence to immunosuppressive therapy. BMC IMMUNOLOGY, 18: 52. ISSN 1471-2172,
Full text not available from this repository. (Request a copy)Abstract
Background: Non-adherence has been associated with reduced graft survival. The aim of this study was to investigate the immunological mechanisms underlying chronic renal allograft rejection using a model of non-adherence to immunosuppressive therapy. We used a MHC (major histocompatibility complex) -mismatched rat model of renal transplantation (Brown Norway to Lewis), in which rats received daily oral cyclosporine A. In analogy to non-adherence to therapy, one group received cyclosporine A on alternating days only. Rejection was histologically graded according to the Banff classification. We quantified fibrosis by trichrome staining and intra-graft infiltration of T cells, B cells, and monocytes/macrophages by immunohistochemistry. The distribution of B lymphocytes was assessed using immunofluorescence microscopy. Intra-graft chemokine, chemokine receptor, BAFF (B cell activating factor belonging to the TNF family), and immunoglobulin G transcription levels were analysed by RT-PCR. Finally, we evaluated donor-specific antibodies (DSA) and complement-dependent cytotoxicity using flow cytometry. Results: After 28 days, cellular rejection occurred during non-adherence in 5/6 animals, mixed with humoral rejection in 3/6 animals. After non-adherence, the number of T lymphocytes were elevated compared to daily immunosuppression. Monocyte numbers declined over time. Accordingly, lymphocyte chemokine transcription was significantly increased in the graft, as was the transcription of BAFF, BAFF receptor, and Immunoglobulin G. Donor specific antibodies were elevated in non-adherence, but did not induce complement-dependent cytotoxicity. Conclusion: Cellular and humoral rejection, lymphocyte infiltration, and de novo DSA are induced in this model of non-adherence.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CELL-ACTIVATING FACTOR; KIDNEY-TRANSPLANT FAILURE; MEDIATED REJECTION; AUTOIMMUNE-DISEASE; SJOGRENS-SYNDROME; IMMUNE-RESPONSE; HLA ANTIBODIES; EXPRESSION; BAFF; NEOGENESIS; Donor specific antibodies; Humoral rejection; Renal transplantation; Non-adherence; Leukocyte infiltration; BAFF |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:18 |
| Last Modified: | 20 Feb 2019 14:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1679 |
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