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, Giorgio Raimondi, D. K C Cooper, M. B. Ezzelarab, A. W. Thomson

Research output: Contribution to journalArticle

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

Fingerprint

Primates
Haplorhini
Lymphoid Tissue
Sirolimus
Antilymphocyte Serum
Macaca fascicularis
Regulatory T-Lymphocytes
Esters
Coloring Agents
Cell Proliferation
Staining and Labeling
T-Lymphocytes

Keywords

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

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)
  • Medicine(all)

Cite this

Sequential monitoring and stability of Ex vivo-expanded autologous and nonautologous regulatory t cells following infusion in nonhuman primates. / Zhang, H.; Guo, H.; Lu, L.; Zahorchak, A. F.; Wiseman, R. W.; Raimondi, Giorgio; Cooper, D. K C; Ezzelarab, M. B.; Thomson, A. W.

In: American Journal of Transplantation, Vol. 15, No. 5, 01.05.2015, p. 1253-1266.

Research output: Contribution to journalArticle

Zhang, H. ; Guo, H. ; Lu, L. ; Zahorchak, A. F. ; Wiseman, R. W. ; Raimondi, Giorgio ; Cooper, D. K C ; Ezzelarab, M. B. ; Thomson, A. W. / Sequential monitoring and stability of Ex vivo-expanded autologous and nonautologous regulatory t cells following infusion in nonhuman primates. In: American Journal of Transplantation. 2015 ; Vol. 15, No. 5. pp. 1253-1266.
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