title: Comparison of regulatory T cells in hemodialysis patients and healthy controls: implications for cell therapy in transplantation.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
authors.affiliation: Medical Research Council Centre for Transplantation, King's College London, King's Health Partners, Guy's Hospital, London, United Kingdom.
authors.forename: Behdad
authors.initials: B
authors.lastname: Afzali
authors.forename: Francis C
authors.initials: FC
authors.lastname: Edozie
authors.forename: Henrieta
authors.initials: H
authors.lastname: Fazekasova
authors.forename: Cristiano
authors.initials: C
authors.lastname: Scottà
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Mitchell
authors.forename: James B
authors.initials: JB
authors.lastname: Canavan
authors.forename: Shahram Y
authors.initials: SY
authors.lastname: Kordasti
authors.forename: Prabhjoat S
authors.initials: PS
authors.lastname: Chana
authors.forename: Richard
authors.initials: R
authors.lastname: Ellis
authors.forename: Graham M
authors.initials: GM
authors.lastname: Lord
authors.forename: Susan
authors.initials: S
authors.lastname: John
authors.forename: Rachel
authors.initials: R
authors.lastname: Hilton
authors.forename: Robert I
authors.initials: RI
authors.lastname: Lechler
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lombardi
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D016219:Immunotherapy, Adoptive; D020381:Interleukin-17 / Q000096:biosynthesis; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D020123:Sirolimus / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D020381:Interleukin-17; D020123:Sirolimus