Sequential monitoring and stability of Ex vivo-expanded autologous and nonautologous regulatory t cells following infusion in nonhuman primates

Academic Article


  • © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons. Ex vivo-expanded cynomolgus monkey CD4+CD25+CD127- regulatory T cells (Treg) maintained Foxp3 demethylation status at the Treg-specific demethylation region, and potently suppressed T cell proliferation through three rounds of expansion. When carboxyfluorescein succinimidyl ester- or violet proliferation dye 450-labeled autologous (auto) and nonautologous (non-auto)-expanded Treg were infused into monkeys, the number of labeled auto-Treg in peripheral blood declined rapidly during the first week, but persisted at low levels in both normal and anti-thymocyte globulin plus rapamycin-treated (immunosuppressed; IS) animals for at least 3 weeks. By contrast, MHC-mismatched non-auto-Treg could not be detected in normal monkey blood or in blood of two out of the three IS monkeys by day 6 postinfusion. They were also more difficult to detect than auto-Treg in peripheral lymphoid tissue. Both auto- and non-auto-Treg maintained Ki67 expression early after infusion. Sequential monitoring revealed that adoptively transferred auto-Treg maintained similarly high levels of Foxp3 and CD25 and low CD127 compared with endogenous Treg, although Foxp3 staining diminished over time in these nontransplanted recipients. Thus, infused ex vivo-expanded auto-Treg persist longer than MHC-mismatched non-auto-Treg in blood of nonhuman primates and can be detected in secondary lymphoid tissue. Host lymphodepletion and rapamycin administration did not consistently prolong the persistence of non-auto-Treg in these sites.
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  • Zhang H; Guo H; Lu L; Zahorchak AF; Wiseman RW; Raimondi G; Cooper DKC; Ezzelarab MB; Thomson AW
  • Start Page

  • 1253
  • End Page

  • 1266
  • Volume

  • 15
  • Issue

  • 5