Long-Term Engraftment of Human Natural T Regulatory Cells in NOD/SCID IL2rγcnull Mice by Expression of Human IL-2

Regulatory T cells are essential to maintain immune homeostasis and prevent autoimmunity. Therapy with in vitro expanded human nTRegs is being tested to prevent graft versus host disease, which is a major cause for morbidity and mortality associated with hematopoietic stem cell transplantation. Thei...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2012-12, Vol.7 (12), p.e51832
Main Authors: Abraham, Sojan, Pahwa, Rajendra, Ye, Chunting, Choi, Jang-gi, Pahwa, Savita, Jaggaiahgari, Shashidhar, Raut, Ashwin, Chen, Shuiping, Manjunath, N., Shankar, Premlata
Format: Article
Language:English
Subjects:
Arteriosclerosis
Autoimmune diseases
Biology
Bone marrow
Cytokines
Genotype & phenotype
Graft-versus-host reaction
Health sciences
Hematopoietic stem cells
Homeostasis
Human behavior
Human performance
Immunoregulation
In vivo methods and tests
Infectious diseases
Interleukin 2
Lymphocytes
Lymphocytes T
Medicine
Morbidity
Organs
Rodents
Stem cell transplantation
Therapy
Transcription factors
Transplantation
Transplants & implants
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Regulatory T cells are essential to maintain immune homeostasis and prevent autoimmunity. Therapy with in vitro expanded human nTRegs is being tested to prevent graft versus host disease, which is a major cause for morbidity and mortality associated with hematopoietic stem cell transplantation. Their usefulness in therapy will depend on their capacity to survive, migrate appropriately and retain suppressive activity when introduced into a transplant recipient. The lack of a suitable animal model for studying the in vivo reconstitutive capability of human nTRegs is a major impediment for investigating the behavior of adoptively transferred nTRegs in vivo. We show that injection of a plasmid encoding human IL-2 is necessary and sufficient for long term engraftment of in vitro expanded nTRegs in NOD-SCID IL2rγcnull mice. We also demonstrate that these in vivo reconstituted TRegs traffic to different organs of the body and retain suppressive function. Finally, in an IL-2 accelerated GVHD model, we show that these in vivo reconstituted TRegs are capable of preventing severe xenogenic response of human PBMCs. Thus, this novel ‘hu-TReg mouse’ model offers a pre-clinical platform to study the in vivo function and stability of human nTRegs and their ability to modulate autoimmune diseases and GVHD.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0051832