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

H. Zhang, H. Guo, L. Lu, A. F. Zahorchak, R. W. Wiseman, G. Raimondi, D. K.C. Cooper, M. B. Ezzelarab, A. W. Thomson

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1253-1266
Number of pages14
JournalAmerican Journal of Transplantation
Volume15
Issue number5
DOIs
StatePublished - May 1 2015
Externally publishedYes

Keywords

  • Immunosuppressant
  • T cell biology
  • animal models: nonhuman primate
  • basic (laboratory) research / science
  • immunobiology
  • immunosuppressant
  • immunosuppression / immune modulation
  • mechanistic target of rapamycin (mTOR)
  • polyclonal preparations: rabbit antithymocyte globulin
  • translational research / science

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Fingerprint

Dive into the research topics of 'Sequential monitoring and stability of Ex vivo-expanded autologous and nonautologous regulatory t cells following infusion in nonhuman primates'. Together they form a unique fingerprint.

Cite this