Induction of Long-Lasting Regulatory B Lymphocytes by Modified Immune Cells in Kidney Transplant Recipients

We recently demonstrated that donor-derived modified immune cells (MICs)-PBMCs that acquire immunosuppressive properties after a brief treatment-induced specific immunosuppression against the allogeneic donor when administered before kidney transplantation. We found up to a 68-fold increase in CD19...

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Bibliographic Details
Published in:Journal of the American Society of Nephrology 2023-01, Vol.34 (1), p.160-174
Main Authors: Morath, Christian, Schaier, Matthias, Ibrahim, Eman, Wang, Lei, Kleist, Christian, Opelz, Gerhard, Süsal, Caner, Ponath, Gerald, Aly, Mostafa, Alvarez, Cristiam M, Kälble, Florian, Speer, Claudius, Benning, Louise, Nusshag, Christian, Pego da Silva, Luiza, Sommerer, Claudia, Hückelhoven-Krauss, Angela, Czock, David, Mehrabi, Arianeb, Schwab, Constantin, Waldherr, Rüdiger, Schnitzler, Paul, Merle, Uta, Tran, Thuong Hien, Scherer, Sabine, Böhmig, Georg A, Müller-Tidow, Carsten, Reiser, Jochen, Zeier, Martin, Schmitt, Michael, Terness, Peter, Schmitt, Anita, Daniel, Volker
Format: Article
Language:English
Subjects:
B-Lymphocytes, Regulatory
Clinical Research
Humans
Immune Tolerance
Immunosuppression Therapy
Immunosuppressive Agents - therapeutic use
Kidney Transplantation
Transplant Recipients
Transplantation
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Summary:We recently demonstrated that donor-derived modified immune cells (MICs)-PBMCs that acquire immunosuppressive properties after a brief treatment-induced specific immunosuppression against the allogeneic donor when administered before kidney transplantation. We found up to a 68-fold increase in CD19 + CD24 hi CD38 hi transitional B lymphocytes compared with transplanted controls. Ten patients from a phase 1 clinical trial who had received MIC infusions before kidney transplantation were followed to post-transplant day 1080. Patients treated with MICs had a favorable clinical course, showing no donor-specific human leukocyte antigen antibodies or acute rejections. The four patients who had received the highest dose of MICs 7 days before surgery and were on reduced immunosuppressive therapy showed an absence of in vitro lymphocyte reactivity against stimulatory donor blood cells, whereas reactivity against third party cells was preserved. In these patients, numbers of transitional B lymphocytes were 75-fold and seven-fold higher than in 12 long-term survivors on minimal immunosuppression and four operationally tolerant patients, respectively ( P
ISSN:1046-6673
1533-3450
DOI:10.1681/ASN.2022020210