Donor bone marrow together with recipient regulatory T cells induces chimerism without irradiation in kidney transplantation.

Authors

Thomas Wekerle, Moritz Muckenhuber, Andreas Heinzel, Anna Marianne Weijler, Ana F David, Verena Kainz, Karin Hu, Jasmin Mucha, Konstantinos Mengrelis, Roman Reindl-Schwaighofer, Georg A Böhmig, Bruno Watschinger, Georg Györi, Thomas Soliman, Andreas Salat, Christoph Schwarz, Marlena Muhm, Georg Heinze, Michael Wolzt, Nina Worel, Michaela Fortschegger, Thomas Lion, Heinz Regele, Gabriela Berlakovich, Philip F Halloran, Matthias Edinger, Rainer Oberbauer

Published in

Science translational medicine. Volume 18. Issue 854. Pages eaee6850. Jun 17, 2026. Epub Jun 17, 2026.

Abstract

Cotransplantation of donor bone marrow (BM) has yielded a therapeutic benefit in clinical trials of kidney transplantation by inducing chimerism-based tolerance, but this was dependent on unfavorable recipient irradiation. Additional regulatory T (T_reg) cell administration can overcome the need for myelosuppression, but this has been demonstrated only in mice so far. Here, we conducted a controlled, phase 1/2a trial of combined BM and T_reg cell therapy in HLA-mismatched living-donor kidney transplantation (NCT03867617). Six patients received polyclonal recipient T_reg cells and donor BM cells (BMCs) immediately posttransplant. Immunosuppression consisted of thymoglobulin, belatacept, sirolimus, steroids, and short-course tocilizumab. The control group received no T_reg cells, BMCs, or tocilizumab. Total leukocyte donor chimerism was detected across all patients in the study group posttransplantation. This was not observed in any patient belonging to the control group, consequently meeting the primary end point of higher chimerism levels in the study versus control groups (P = 0.001). Chimerism was observed across multiple lineages, with up to 4% in T cells. For three patients in the study group, immunosuppression could be minimized to belatacept monotherapy. Antidonor reactivity was decreased in in vitro T cell proliferation assays, suggesting specific downmodulation of the antidonor T cell response. In addition, expansion of antidonor T cell clones was shown by T cell receptor sequencing analysis to be dampened in the study versus control groups. This trial serves as a proof of concept for a combination cell therapy that induces chimerism-based immunomodulation in kidney transplantation without the need for irradiation.

PMID:
42308328
Bibliographic data and abstract were imported from PubMed on 18 Jun 2026.

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