Characterization, biology, and expansion of regulatory T cells in the Cynomolgus macaque for preclinical studies.
animal models: nonhuman primate
basic (laboratory) research/science
cellular transplantation (nonislet)
graft survival
immune regulation
immunobiology
immunosuppression/immune modulation
tolerance: chimerism
translational research/science
Journal
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
ISSN: 1600-6143
Titre abrégé: Am J Transplant
Pays: United States
ID NLM: 100968638
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
05
09
2018
revised:
16
01
2019
accepted:
04
02
2019
pubmed:
16
2
2019
medline:
1
9
2020
entrez:
16
2
2019
Statut:
ppublish
Résumé
Reliable in vitro expansion protocols of regulatory T cells (Tregs) are needed for clinical use. We studied the biology of Mauritian Cynomolgus macaque (MCM) Tregs and developed four in vitro Treg expansion protocols for translational studies. Tregs expanded 3000-fold when artificial antigen presenting cells (aAPCs) expressing human CD80, CD58 and CD32 were used throughout the culture. When donor peripheral blood mononuclear cells (PBMCs) were used as the single source of APCs followed by aAPCs, Tregs expanded 2000-fold. Tregs from all protocols suppressed the proliferation of anti-CD2CD3CD28 bead-stimulated autologous PBMCs albeit with different potencies, varying from 1:2-1:4 Treg:PBMC ratios, up to >1:32. Reculture of cryopreserved Tregs permitted reexpansion with improved suppressive activity. Occasionally, CD8 contamination was observed and resolved by resorting. Specificity studies showed greater suppression of stimulation by anti-CD2CD3CD28 beads of PBMCs from the same donor used for stimulation during the Treg cultures and of autologous cells than of third-party PBMC responders. Similar to humans, the Treg-specific demethylated region (TSDR) within the Foxp3 locus correlated with suppressive activity and expression of Foxp3. Contrary to humans, FoxP3 expression did not correlate with CD45RA or CD127 expression. In summary, we have characterized MCM Tregs and developed four Treg expansion protocols that can be used for preclinical applications.
Identifiants
pubmed: 30768842
doi: 10.1111/ajt.15313
pmc: PMC6658340
mid: NIHMS1011949
pii: S1600-6135(22)09185-7
doi:
Substances chimiques
FOXP3 protein, human
0
Forkhead Transcription Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2186-2198Subventions
Organisme : Columbia University Departments of Medicine and Surgery
Pays : International
Organisme : Columbia University Core award
Pays : International
Organisme : Irving Pilot Translational Science award for new investigators
Pays : International
Organisme : NIH HHS
ID : R01 OD017949
Pays : United States
Organisme : NIH HHS
ID : S10 OD020056
Pays : United States
Organisme : Banting Foundation
Pays : International
Informations de copyright
© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.
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