title: Long-term engraftment of human natural T regulatory cells in NOD/SCID IL2rγc(null) mice by expression of human IL-2.
abstract: Regulatory T cells are essential to maintain immune homeostasis and prevent autoimmunity. Therapy with in vitro expanded human nT(Regs) 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 nT(Regs) is a major impediment for investigating the behavior of adoptively transferred nT(Regs)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 nT(Regs) in NOD-SCID IL2rγc(null) mice. We also demonstrate that these in vivo reconstituted T(Regs) 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 T(Regs) are capable of preventing severe xenogenic response of human PBMCs. Thus, this novel 'hu-T(Reg) mouse' model offers a pre-clinical platform to study the in vivo function and stability of human nT(Regs) and their ability to modulate autoimmune diseases and GVHD.
authors.affiliation: Department of Biomedical Sciences, Center of Excellence in Infectious Disease Research, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas, United States of America.
authors.forename: Sojan
authors.initials: S
authors.lastname: Abraham
authors.forename: Rajendra
authors.initials: R
authors.lastname: Pahwa
authors.forename: Chunting
authors.initials: C
authors.lastname: Ye
authors.forename: Jang-Gi
authors.initials: JG
authors.lastname: Choi
authors.forename: Savita
authors.initials: S
authors.lastname: Pahwa
authors.forename: Shashidhar
authors.initials: S
authors.lastname: Jaggaiahgari
authors.forename: Ashwin
authors.initials: A
authors.lastname: Raut
authors.forename: Shuiping
authors.initials: S
authors.lastname: Chen
authors.forename: N
authors.initials: N
authors.lastname: Manjunath
authors.forename: Premlata
authors.initials: P
authors.lastname: Shankar
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control; D004195:Disease Models, Animal; D015870:Gene Expression; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D010641:Phenotype; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation*; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D007376:Interleukin-2