David, Ana F. and Heinzel, Andreas and Kammer, Michael and Aschauer, Constantin and Reindl-Schwaighofer, Roman and Hu, Karin and Chen, Hao-Shan and Muckenhuber, Moritz and Kubetz, Anna and Weijler, Anna Marianne and Worel, Nina and Edinger, Matthias and Berlakovich, Gabriela and Lion, Thomas and Sykes, Megan and Wekerle, Thomas and Oberbauer, Rainer (2024) Combination cell therapy leads to clonal deletion of donor-speci fi c T cells in kidney transplant recipients. EBIOMEDICINE, 106: 105239. ISSN 2352-3964
Full text not available from this repository. (Request a copy)Abstract
Background Induction of donor-speci fi c tolerance is a promising approach to achieve long-term graft patency in transplantation with little to no maintenance immunosuppression. Changes to the recipient ' s T cell receptor (TCR) repertoire are understood to play a pivotal role in the establishment of a robust state of tolerance in chimerism-based transplantation protocols. Methods We investigated changes to the TCR repertoires of patients participating in an ongoing prospective, controlled, phase I/IIa trial designed to evaluate the safety and ef fi cacy of combination cell therapy in living donor kidney transplantation. Using high-throughput sequencing, we characterized the repertoires of six kidney recipients who also received bone marrow from the same donor (CKBMT), together with an infusion of polyclonal autologous Treg cells instead of myelosuppression. Findings Patients undergoing combination cell therapy exhibited partial clonal deletion of donor-reactive CD4 + T cells at one, three, and six months post-transplant, compared to control patients receiving the same immunosuppression regimen but no cell therapy (p = 0.024). The clonality, R20 and turnover rates of the CD4 + and CD8 + TCR repertoires were comparable in both groups, showing our protocol caused no excessive repertoire shift or loss of diversity. Treg clonality was lower in the case group than in control (p = 0.033), suggesting combination cell therapy helps to preserve Treg diversity. Interpretation Overall, our data indicate that combining Treg cell therapy with CKBMT dampens the alloimmune response to transplanted kidneys in humans in the absence of myelosuppression. Funding This study was funded by the Vienna Science and Technology Fund (WWTF).
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | REPERTOIRE; CHIMERISM; TOLERANCE; DIVERSITY; T cell receptor; Alloreactivity; Kidney transplantation; Cell therapy; Immunological tolerance |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Jan 2026 06:54 |
| Last Modified: | 14 Jan 2026 06:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/64503 |
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