@article{cdb057940a7846fca0ed4a5cce9c1a7c,
title = "Characterization, biology, and expansion of regulatory T cells in the Cynomolgus macaque for preclinical studies",
abstract = "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.",
keywords = "animal models, nonhuman primate, basic (laboratory) research, science, cellular transplantation (nonislet), graft survival, immune regulation, immunobiology, immunosuppression, immune modulation, tolerance, chimerism, translational research, IN-VITRO, HEMATOPOIETIC CHIMERISM, ALLOGRAFT TOLERANCE, THERAPY, FOXP3, EXPRESSION, HAPLOTYPES, INFUSION, SURVIVAL, BETA",
author = "Paula Alonso-Guallart and Zitsman, {Jonah S.} and Jeffrey Stern and Kofman, {Sigal B.} and David Woodland and Siu-Hong Ho and Sondermeijer, {Hugo P.} and Leo Buhler and Adam Griesemer and Megan Sykes and Raimon Duran-Struuck",
note = "Funding Information: British Columbia, Vancouver, Canada. Funding for these studies was provided by NIH grant R01OD017949, by startup funds from the Columbia University Departments of Medicine and Surgery (to MS and RDS), the Banting Foundation (to MS), the Columbia University Core award (to RDS), and the Irving Pilot Translational Science award for new investigators (to RDS). Research reported in this publication was performed in the CCTI Flow Cytometry Core, supported in part by the Office of the Director, National Institutes of Health under the award S10OD020056. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.` Funding Information: Artificial antigen-presenting cells (aAPC) that express CD80, CD58 and CD32 were kindly provided by Dr. Megan Levings, University of British Columbia, Vancouver, Canada. Funding for these studies was provided by NIH grant R01OD017949, by startup funds from the Columbia University Departments of Medicine and Surgery (to MS and RDS), the Banting Foundation (to MS), the Columbia University Core award (to RDS), and the Irving Pilot Translational Science award for new investigators (to RDS). Research reported in this publication was performed in the CCTI Flow Cytometry Core, supported in part by the Office of the Director, National Institutes of Health under the award S10OD020056. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.` Funding Information: NIH; Columbia University Departments of Medicine and Surgery; Banting Foundation; Columbia University Core award; Irving Pilot Translational Science award for new investigators Publisher Copyright: {\textcopyright} 2019 The American Society of Transplantation and the American Society of Transplant Surgeons",
year = "2019",
month = aug,
doi = "10.1111/ajt.15313",
language = "English",
volume = "19",
pages = "2186--2198",
journal = "American Journal of Transplantation",
issn = "1600-6135",
publisher = "Wiley",
number = "8",
}