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Open Access 01-12-2017 | Research article

Renal allograft rejection, lymphocyte infiltration, and de novo donor-specific antibodies in a novel model of non-adherence to immunosuppressive therapy

Authors: Louisa Kühne, Bettina Jung, Helen Poth, Antonia Schuster, Simone Wurm, Petra Ruemmele, Bernhard Banas, Tobias Bergler

Published in: BMC Immunology | Issue 1/2017

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.

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Title: Renal allograft rejection, lymphocyte infiltration, and de novo donor-specific antibodies in a novel model of non-adherence to immunosuppressive therapy
Authors: Louisa Kühne
Bettina Jung
Helen Poth
Antonia Schuster
Simone Wurm
Petra Ruemmele
Bernhard Banas
Tobias Bergler
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: BMC Immunology / Issue 1/2017
Electronic ISSN: 1471-2172
DOI: https://doi.org/10.1186/s12865-017-0236-6

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Background

Results

Conclusion

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