A novel combined cellular therapy for kidney transplantation helps to reduce donor-specific responses to the transplanted organ without the need for maintenance triple immunosuppression. The overall diversity of the T cell receptor repertoire, which is important for immune defense, is preserved. This has been shown by an international study led by the Medical University of Vienna and recently published in the Lancet Discovery Science series eBioMedicine.
Typically, patients must take maintenance immunosuppressants for the rest of their lives after a transplant to prevent their immune system from rejecting the new organ. The new approach the research team is investigating combines bone marrow cells from the donor with specialized immune cells (Treg cells) from the recipient. The results come from an ongoing clinical trial investigating the safety and efficacy of the combination therapy.
Researchers led by Rainer Oberbauer (Division of Nephrology and Dialysis, Department of Medical Sciences III), in collaboration with Thomas Wöckerle (Division of Transplantation, Department of General Surgery) at the Medical University of Vienna, used a complex technique (high-throughput sequencing) to analyze changes in the TCR repertoire in six kidney transplant recipients. In addition to the donor organ, they also received bone marrow from the same donor and, instead of the usual myelosuppression (reduction of bone marrow function), they also received an infusion of polyclonal (containing many different T cell receptors) autologous Treg cells. The TCR repertoire is the sum of an individual's different T cell receptors (TCRs). This diversity is crucial for the immune system's ability to recognize and respond to a wide range of antigens.
In transplant patients, the combined cell therapy reduced T cells that could react to the donor organ by targeted ablation. “Overall, our data show that combining Treg cell therapy with combined kidney and bone marrow transplantation selectively reduces immune responses to transplanted kidneys in humans,” the study authors explain. The findings may help future studies to further pursue this therapy as a promising approach to transplantation.
The research was funded by the Vienna Science and Technology Fund (WWTF) and published in the scientific journal eBioMedicine.
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Journal References:
David, A.F., etc (2024). Combined cell therapy leads to clonal deletion of donor-specific T cells in kidney transplant patients. Electronic Biomedicine. doi.org/10.1016/j.ebiom.2024.105239.
