scholarly journals Ex Vivo Expanded Human Regulatory T Cells Can Prolong Survival of a Human Islet Allograft in a Humanized Mouse Model

2013 ◽  
Vol 96 (8) ◽  
pp. 707-716 ◽  
Author(s):  
Douglas C. Wu ◽  
Joanna Hester ◽  
Satish N. Nadig ◽  
Wei Zhang ◽  
Piotr Trzonkowski ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Mouse Model ◽  
Ex Vivo ◽  
Human Islet ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
Islet Allograft

scholarly journals Ex Vivo–Expanded Human Regulatory T Cells Prevent the Rejection of Skin Allografts in a Humanized Mouse Model

2010 ◽  
Vol 90 (12) ◽  
pp. 1321-1327 ◽  
Author(s):  
Fadi Issa ◽  
Joanna Hester ◽  
Ryoichi Goto ◽  
Satish N. Nadig ◽  
Tim E. Goodacre ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Mouse Model ◽  
Ex Vivo ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
Skin Allografts

Cellular immunotherapy with ex vivo expanded cord blood T cells in a humanized mouse model of EBV-associated lymphoproliferative disease

Immunotherapy ◽  
2015 ◽  
Vol 7 (4) ◽  
pp. 335-341 ◽  
Author(s):  
Go Matsuda ◽  
Ken-Ichi Imadome ◽  
Fuyuko Kawano ◽  
Masashi Mochizuki ◽  
Nakaba Ochiai ◽  
...  
Keyword(s):  
T Cells ◽  
Mouse Model ◽  
Cord Blood ◽  
Ex Vivo ◽  
Lymphoproliferative Disease ◽  
Cellular Immunotherapy ◽  
Humanized Mouse ◽  
Humanized Mouse Model

scholarly journals Intradermal injection of low dose human regulatory T cells inhibits skin inflammation in a humanized mouse model

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Sija Landman ◽  
Vivian L. de Oliveira ◽  
Piet E. J. van Erp ◽  
Esther Fasse ◽  
Stijn C. G. Bauland ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Mouse Model ◽  
Low Dose ◽  
Skin Inflammation ◽  
Intradermal Injection ◽  
Humanized Mouse ◽  
Humanized Mouse Model

scholarly journals Regulatory T Cells Prevent Liver Fibrosis During HIV Type 1 Infection in a Humanized Mouse Model

2013 ◽  
Vol 209 (7) ◽  
pp. 1039-1044 ◽  
Author(s):  
Jun-ichi Nunoya ◽  
Michael L. Washburn ◽  
Grigoriy I. Kovalev ◽  
Lishan Su
Keyword(s):  
T Cells ◽  
Liver Fibrosis ◽  
Regulatory T Cells ◽  
Mouse Model ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
Hiv Type 1

scholarly journals Humanized Mouse Model of HIV-1 Latency with Enrichment of Latent Virus in PD-1+and TIGIT+CD4 T Cells

2019 ◽  
Vol 93 (10) ◽  
Author(s):  
George N. Llewellyn ◽  
Eduardo Seclén ◽  
Stephen Wietgrefe ◽  
Siyu Liu ◽  
Morgan Chateau ◽  
...  
Keyword(s):  
T Cells ◽  
Mouse Model ◽  
Ex Vivo ◽  
Latent Reservoir ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
Latently Infected ◽  
Infected Cells ◽  
Latent Hiv ◽  
Hiv 1

ABSTRACTCombination anti-retroviral drug therapy (ART) potently suppresses HIV-1 replication but does not result in virus eradication or a cure. A major contributing factor is the long-term persistence of a reservoir of latently infected cells. To study this reservoir, we established a humanized mouse model of HIV-1 infection and ART suppression based on an oral ART regimen. Similar to humans, HIV-1 levels in the blood of ART-treated animals were frequently suppressed below the limits of detection. However, the limited timeframe of the mouse model and the small volume of available samples makes it a challenging model with which to achieve full viral suppression and to investigate the latent reservoir. We therefore used anex vivolatency reactivation assay that allows a semiquantitative measure of the latent reservoir that establishes in individual animals, regardless of whether they are treated with ART. Using this assay, we found that latently infected human CD4 T cells can be readily detected in mouse lymphoid tissues and that latent HIV-1 was enriched in populations expressing markers of T cell exhaustion, PD-1 and TIGIT. In addition, we were able to use theex vivolatency reactivation assay to demonstrate that HIV-specific TALENs can reduce the fraction of reactivatable virus in the latently infected cell population that establishesin vivo, supporting the use of targeted nuclease-based approaches for an HIV-1 cure.IMPORTANCEHIV-1 can establish latent infections that are not cleared by current antiretroviral drugs or the body’s immune responses and therefore represent a major barrier to curing HIV-infected individuals. However, the lack of expression of viral antigens on latently infected cells makes them difficult to identify or study. Here, we describe a humanized mouse model that can be used to detect latent but reactivatable HIV-1 in both untreated mice and those on ART and therefore provides a simple system with which to study the latent HIV-1 reservoir and the impact of interventions aimed at reducing it.

HUMAN REGULATORY T CELLS PREVENT ISLET ALLOGRAFT REJECTION

2008 ◽  
Vol 31 (4) ◽  
pp. 25
Author(s):  
Douglas C Wu ◽  
Joanna Wieckiewicz ◽  
Kathryn J Wood
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Islet Transplantation ◽  
Pancreatic Islet ◽  
Allograft Rejection ◽  
Ex Vivo ◽  
Human Islets ◽  
Human Islet ◽  
Pancreatic Islet Transplantation ◽  
Islet Allograft

Background: Type 1 diabetes mellitus represents a significant burden on global healthcare. Pancreatic islet transplantation offers an effective means of controlling the disease, but shortage of donor tissue, graft thrombosis, and immunological rejection after transplantation remain obstacles that need to be overcome. Our aim was to assess the ability of ex vivo expanded human regulatory T cells (Treg) in modulating the rejection response against a human islet allograft in a clinically relevant model of human pancreatic islet transplantation. Methods: We studied the rejection response against allogeneic human islets in acohort of 32 immunodeficient mice which had been reconstituted with a functional human immune system. Thirteen subjects were transplanted with human islets without further immunological modification; graft survival was compared with that of thirteen subjects treated additionally with human regulatory T cells. Six controls were given a human islet transplant, but not reconstituted with human immune cells to demonstrate the functionality of the islet graft in the absence of immunological rejection. Graft function was assessed with serial blood glucose measurements, immunohistochemistry,immunoflourescence, and flow cytometry. Findings: Human islet allografts were rapidly rejected in subjects that did notreceive Treg. With Treg treatment, however, human islet allograft rejection was prevented (median survival time (MST) of > 45 days with Treg, as opposed to an MST of 23 days without Treg). Ex vivo expanded Treg homed to the lymphoid tissue draining the graft site where they suppressed the priming, activation, proliferation, and effector cytokine production of alloreactive T cells. Interpretation: These findings in a clinically relevant model of human pancreatic islet transplantation demonstrate the ability of ex vivo expanded human Treg to attenuate acute islet allograft rejection, and provide further support for their use in cellular immunotherapy.

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