A new combination therapy for kidney transplants can help reduce the body’s defense reactions against the transplanted organ without the need for strong suppression of the immune system. The diversity and breadth of the T cell receptor repertoire, which are important for the immune system, are retained. This was shown by an international study led by the Medical University of Vienna, which was recently published in the specialist journal “eBioMedicine” in the Lancet Discovery Science series.
Normally, patients have to take strong medications after a transplant to prevent their immune system from rejecting the new organ. The new approach investigated by the study team uses a combination of bone marrow cells from the donor and special immune cells (Treg cells) from the recipient. The results come from an ongoing clinical trial investigating the safety and effectiveness of the combination therapy.
Using a complex technique (high-throughput sequencing), the researchers around Rainer Oberbauer (Clinical Department of Nephrology and Dialysis, University Department of Internal Medicine III) in cooperation with Thomas Wekerle (Department of Transplantation, University Department of General Surgery) from MedUni Vienna, together with partners from Austria, Germany and the USA, characterized the changes in the TCR repertoires of six kidney transplant recipients. In addition to the donor organ, these recipients had also received bone marrow from the same donor and an infusion of polyclonal (with a variety of different T cell receptors) autologous Treg cells, instead of the usual myelosuppression (reduction in bone marrow function). The TCR repertoire is the totality of the different T cell receptors (TCRs) in an individual. This diversity is crucial for the immune system’s ability to recognize and respond to a wide range of antigens.
Immune response reduced
The combined cell therapy resulted in the T cells that can react against the donor organ being reduced in the transplant patients by targeted removal (selective deletion). “Overall, our data show that the combination of Treg cell therapy with combined kidney and bone marrow transplantation reduces the immune response to transplanted kidneys in humans,” explain the study authors. The results of this study can help to pursue this therapeutic method as a promising avenue in transplantation in further studies.
The study was funded by the Vienna Science, Research and Technology Fund (WWTF) and published in the journal “eBioMedicine”.
Publication: eBioMedicine
Combination cell therapy leads to clonal deletion of donor-specific T cells in kidney transplant recipients
Ana F. David, Andreas Heinzel, Michael Kammer, Constantin Aschauer, Roman Reindl-Schwaighofer, Karin Hu, Hao-Shan Chen, Moritz Muckenhuber, Anna Kubetz, Anna Marianne Weijler, Nina Worel, Matthias Edinger, Gabriela Berlakovich, Thomas Lion, Megan Sykes, Thomas Wekerle, Rainer Oberbauer
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