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

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Abstract

BACKGROUND AND OBJECTIVES: Cell-based therapy with natural (CD4(+)CD25(hi)CD127(lo)) 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
Number of pages10
JournalClinical Journal Of The American Society Of Nephrology
Volume8
Issue number8
DOIs
Publication statusPublished - 31 Jul 2013

Keywords

  • STAGE RENAL-FAILURE
  • IN-VITRO
  • KIDNEY-TRANSPLANTATION
  • TOLERANCE
  • RAPAMYCIN
  • SUPPRESSION
  • EXPANSION
  • RESPONSES
  • MTOR
  • IMMUNIZATION

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