| Title: |
Regulatory T cell therapy is associated with distinct immune regulatory lymphocytic infiltrates in kidney transplants |
| Authors: |
McCallion, O; Cross, AR; Brook, MO; Hennessy, C; Ferreira, R; Trzupek, D; Mulley, WR; Kumar, S; Soares, M; Roberts, IS; Friend, PJ; Lombardi, G; Wood, KJ; Harden, PN; Hester, J; Issa, F |
| Publisher Information: |
Cell Press |
| Publication Year: |
2025 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
Background: Adoptive transfer of autologous regulatory T cells (Tregs) is a promising therapeutic strategy aimed at enabling immunosuppression minimization following kidney transplantation. In our phase 1 clinical trial of Treg therapy in living donor renal transplantation, the ONE Study (ClinicalTrials.gov: NCT02129881), we observed focal lymphocytic infiltrates in protocol kidney transplant biopsies that are not regularly seen in biopsies of patients receiving standard immunosuppression. Methods: We present 7 years of follow-up data on patients treated with adoptive Treg therapy early post-transplantation who exhibited focal lymphocytic infiltrates on a 9-month protocol biopsy. We phenotyped their adoptively transferred and peripherally circulating Treg compartments using CITE-seq and investigated the focal lymphocytic infiltrates with spatial proteomic and transcriptomic technologies. Findings: Graft survival rates were not significantly different between Treg-treated patients and the control reference group. None of the Treg-treated patients experienced clinical rejection episodes or developed de novo donor-specific antibodies, and three of ten successfully reduced their immunosuppression to tacrolimus monotherapy. All Treg-treated patients who underwent a protocol biopsy 9 months post-transplantation exhibited focal lymphocytic infiltrates. Spatial profiling analysis revealed prominent CD20+ B cell and regulatory (IKZF2, IL10, PD-L1, TIGIT) signatures within cell-therapy-associated immune infiltrates, distinct from the pro-inflammatory myeloid signature associated with rejection biopsies. Conclusions: We demonstrate for the first time that immune cell infiltrates in transplanted kidneys can occur following adoptive Treg therapy in humans, potentially facilitating within-graft T:B cell interactions that promote local immune regulation. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doi.org/10.1016/j.medj.2024.11.014 |
| DOI: |
10.1016/j.medj.2024.11.014 |
| Availability: |
https://doi.org/10.1016/j.medj.2024.11.014; https://ora.ox.ac.uk/objects/uuid:8e144f5d-ed21-42a1-b96e-c521b5834208 |
| Rights: |
info:eu-repo/semantics/openAccess ; CC Attribution (CC BY) |
| Accession Number: |
edsbas.419E81A5 |
| Database: |
BASE |