Plasticity and Overlap of In Vitro–Induced Regulatory T-Cell Markers in Healthy Humans

2013 ◽  
Vol 45 (5) ◽  
pp. 1816-1821 ◽  
Author(s):  
H. Wang ◽  
V. Daniel ◽  
M. Sadeghi ◽  
G. Opelz
2012 ◽  
Vol 94 (10S) ◽  
pp. 1160
Author(s):  
H. Wang ◽  
V. Daniel ◽  
M. Sadeghi ◽  
G. Opelz

2015 ◽  
Vol 24 (2) ◽  
pp. 276-284 ◽  
Author(s):  
Daniela Fanigliulo ◽  
Pietro Enea Lazzerini ◽  
Pier Leopoldo Capecchi ◽  
Cristina Ulivieri ◽  
Cosima Tatiana Baldari ◽  
...  

2020 ◽  
Vol 88 (11) ◽  
Author(s):  
Emily M. Siebers ◽  
Elizabeth S. Liedhegner ◽  
Michael W. Lawlor ◽  
Ronald F. Schell ◽  
Dean T. Nardelli

ABSTRACT The symptoms of Lyme disease are caused by inflammation induced by species of the Borrelia burgdorferi sensu lato complex. The various presentations of Lyme disease in the population suggest that differences exist in the intensity and regulation of the host response to the spirochete. Previous work has described correlations between the presence of regulatory T cells and recovery from Lyme arthritis. However, the effects of Foxp3-expressing CD4+ T cells existing prior to, and during, B. burgdorferi infection have not been well characterized. Here, we used C57BL/6 “depletion of regulatory T cell” mice to assess the effects these cells have on the arthritis-resistant phenotype characteristic of this mouse strain. We showed that depletion of regulatory T cells prior to infection with B. burgdorferi resulted in sustained swelling, as well as histopathological changes, of the tibiotarsal joints that were not observed in infected control mice. Additionally, in vitro stimulation of splenocytes from these regulatory T cell-depleted mice resulted in increases in gamma interferon and interleukin-17 production and decreases in interleukin-10 production that were not evident among splenocytes of infected mice in which Treg cells were not depleted. Depletion of regulatory T cells at various times after infection also induced rapid joint swelling. Collectively, these findings provide evidence that regulatory T cells existing at the time of, and possibly after, B. burgdorferi infection may play an important role in limiting the development of arthritis.


2019 ◽  
Vol 206 ◽  
pp. 41-48
Author(s):  
Haruki Katsumata ◽  
Masako Ikemiyagi ◽  
Toshihito Hirai ◽  
Taichi Kanzawa ◽  
Rumi ishii ◽  
...  

2020 ◽  
Author(s):  
JL Reading ◽  
VD Roobrouck ◽  
CM Hull ◽  
PD Becker ◽  
J Beyens ◽  
...  

AbstractRecent clinical experience has demonstrated that adoptive regulatory T cell therapy is a safe and feasible strategy to suppress immunopathology via induction of host tolerance to allo- and autoantigens. However, clinical trials continue to be compromised due to an inability to manufacture a sufficient Treg cell dose. Multipotent adult progenitor cells (MAPCⓇ) promote regulatory T cell differentiation in vitro, suggesting they may be repurposed to enhance ex vivo expansion of Tregs for adoptive cellular therapy. Here, we use a GMP compatible Treg expansion platform to demonstrate that MAPC cell-co-cultured Tregs (MulTreg) exhibit a log-fold increase in yield across two independent cohorts, reducing time to target dose by an average of 30%. Enhanced expansion is linked with a distinct Treg cell-intrinsic transcriptional program, characterized by diminished levels of core exhaustion (BATF, ID2, PRDM1, LAYN, DUSP1), and quiescence (TOB1, TSC22D3) related genes, coupled to elevated expression of cell-cycle and proliferation loci (MKI67, CDK1, AURKA, AURKB). In addition, MulTreg display a unique gut homing (CCR7lo β7hi) phenotype and importantly, are more readily expanded from patients with autoimmune disease compared to matched Treg lines, suggesting clinical utility in gut and/or Th1-driven pathology associated with autoimmunity or transplantation. Relative to expanded Tregs, MulTreg retain equivalent and robust purity, FoxP3 TSDR demethylation, nominal effector cytokine production and potent suppression of Th1-driven antigen specific and polyclonal responses in vitro and xeno graft vs host disease (xGvHD) in vivo. These data support the use of MAPC cell co-culture in adoptive Treg therapy platforms as a means to rescue expansion failure and reduce the time required to manufacture a stable, potently suppressive product.


2012 ◽  
Vol 94 (2) ◽  
pp. 123-131 ◽  
Author(s):  
Céline Miroux ◽  
Olivier Morales ◽  
Khaldoun Ghazal ◽  
Samia Ben Othman ◽  
Yvan de Launoit ◽  
...  

2006 ◽  
Vol 119 ◽  
pp. S194
Author(s):  
Celine Silva Lages ◽  
Paula Velilla ◽  
Gregg Warshaw ◽  
Bin Huang ◽  
Claire Chougnet

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Xinjing Liu ◽  
Ruiyao Hu ◽  
Lulu Pei ◽  
Yuming Xu ◽  
Bo Song

Background: The interleukin (IL)-33 could promote proliferation of regulatory T lymphocytes (Tregs) which are negatively related with brain damage after ischemic stroke. How IL-33 works on Tregs after stroke is unclear. The purpose of this study was to investigate the role of IL-33 for Tregs-mediated neuroprotection and further expounded the mechanisms of protection in mice. Methods: In vitro study, primary mice neuronal cells were subjected to 3h oxygen-glucose deprivation (OGD). The vehicle or drug conditioned Tregs were applied to neurons at the time of induction of hypoxia respectively. Neuronal apoptosis, Tregs related cytokines were measured by MTT assay, Western blotting and enzyme-linked immune-sorbent assay (ELISA). In vivo study, Tregs were depleted by intraperitoneal administration of anti-CD25Ab. Intraperitoneal injection of IL-33 immediately post 60 min transient middle cerebral artery occlusion (tMCAO) modeling. The neurological function test at days 1, 3, 5, 7 and 14 after tMCAO. Infarct volume, Brain edema, cell death, percentage of Tregs and related cytokines were respectively measured by 2,3,5-triphenyltetrazolium chloride or MAP2 staining, dry-wet method, TUNEL staining, flow cytometry and immunofluorescence, Western blotting and ELISA. Results: The supernatant of IL-33-treated Tregs reduced neuronal apoptosis in the OGD model meanwhile elevated the production of Tregs related cytokines IL-10, IL-35 and TGF- β in vitro. Intraperitoneal administration of IL-33 significantly reduced infarct volume and stroke-induced cell death and improved sensorimotor functions. Notably, the protective effect of IL-33 was abolished in mice depleted of Tregs. IL-33 increased CD4+CD25+Foxp3+ Tregs in spleens, blood, and brain in vivo. Yet, ST2 blocking muted these IL-33 activities. Mechanistically, the protection of IL-33 was associated with reduced apoptosis protein and production of Tregs related cytokine. Conclusions: This study elucidated that IL-33 afforded neuroprotection against ischemic brain injury by enhancing ST2-dependent regulatory T-cell expansion and activation, which suggested a promising immune modulatory target for the treatment of stroke.


2017 ◽  
Vol 185 ◽  
pp. 56-63 ◽  
Author(s):  
Haider H. Mohammed Ali ◽  
Nadzieja Drela
Keyword(s):  
T Cell ◽  
B Cells ◽  

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