Comparison of Regulatory T Cells in Hemodialysis Patients and Healthy Controls: Implications for Cell Therapy in Transplantation

Behdad Afzali, Francis C. Edozie, Henrieta Fazekasova, Cristiano Scottà, Peter J. Mitchell, James B. Canavan, Shahram Y. Kordasti, Prabhjoat S. Chana, Richard Ellis, Graham M. Lord, Susan John, Rachel Hilton, Robert I. Lechler, Giovanna Lombardi

Research output: Contribution to journalArticlepeer-review

Abstract

Background and objectives Cell-based therapy with natural (CD4+CD25hiCD127lo) regulatory T cells to induce transplant tolerance is now technically feasible. However, regulatory T cells from hemodialysis patients awaiting transplantation may be functionally/numerically defective. Human regulatory T cells are also heterogeneous, and some are able to convert to proinflammatory Th17 cells. This study addresses the suitability of regulatory T cells from hemodialysis patients for cell-based therapy in preparation for the first clinical trials in renal transplant recipients (the ONE Study). Design, setting, participants, & measurements Healthy controls and age- and sex-matched hemodialysis patients without recent illness/autoimmune disease on established, complication-free hemodialysis for a minimum of 6 months were recruited. Circulating regulatory T cells were studied by flow cytometry to compare the regulatory T cell subpopulations. Regulatory T cells from members of each group were compared for suppressive function and plasticity (IL-17–producing capacity) before and after in vitro expansion with and without Rapamycin, using standard assays. Results Both groups had similar total regulatory T cells and subpopulations I and III. In each subpopulation, regulatory T cells expressed similar levels of the function-associated markers CD27, CD39, HLA-DR, and FOXP3. Hemodialysis regulatory T cells were less suppressive, expanded poorly compared with healthy control regulatory T cells, and produced IL-17 in the absence of Rapamycin. However, Rapamycin efficiently expanded hemodialysis regulatory T cells to a functional and stable cell product. Conclusions Rapamycin-based expansion protocols should enable clinical trials of cell-based immunotherapy for the induction of tolerance to renal allografts using hemodialysis regulatory T cells.
Original languageEnglish
Pages (from-to)1396-1405
JournalClinical Journal of the American Society of Nephrology
Volume8
Issue number8
DOIs
Publication statusPublished - 7 Aug 2013

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