1. Induction of Long-Lasting Regulatory B Lymphocytes by Modified Immune Cells in Kidney Transplant Recipients
- Author
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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, and Daniel, Volker
- Abstract
In previous work, the authors demonstrated that kidney transplant recipients developed donor-specific unresponsiveness when they were given a pretransplant infusion of modified donor-derived PBMCs. In this study, they provide evidence that the immunosuppressive properties of these cells persist and the donor-specific unresponsiveness is long-lasting. In the four patients who received the highest dose of the modified immune cells, administration of these cells was associated with a striking increase in IL-10–producing regulatory B lymphocytes and evidence of the consensus gene expression signature of operational tolerance. In vitro, donor-specific unresponsiveness was abolished after B lymphocyte depletion, suggesting a direct pathophysiologic role for regulatory B lymphocytes. These findings support the notion that modified donor-derived PBMCs may be useful in kidney transplantation, but this approach requires further validation and rigorous controlled randomized studies.
- Published
- 2023
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