creators_name: Tyagi, Rajeev K
creators_name: Jacobse, Justin
creators_name: Li, Jing
creators_name: Allaman, Margret M.
creators_name: Otipoby, Kevin L.
creators_name: Sampson, Erik R.
creators_name: Wilson, K T
creators_name: Goettel, Jeremy A.
type: article
datestamp: 2021-03-26 04:19:01
lastmod: 2021-03-26 04:19:01
metadata_visibility: show
title: HLA-Restriction of Human Treg Cells Is Not Required for Therapeutic Efficacy of Low-Dose IL-2 in Humanized Mice
ispublished: pub
subjects: QR180
keywords:  IBD; IL-2; Tregs; colitis; humanized.
note: Open Access
abstract: Regulatory T (T-reg) cells are essential to maintain immune homeostasis in the intestine and T-reg cell dysfunction is associated with several inflammatory and autoimmune disorders including inflammatory bowel disease (IBD). Efforts using low-dose (LD) interleukin-2 (IL-2) to expand autologous T-reg cells show therapeutic efficacy for several inflammatory conditions. Whether LD IL-2 is an effective strategy for treating patients with IBD is unknown. Recently, we demonstrated that LD IL-2 was protective against experimental colitis in immune humanized mice in which human CD4(+) T cells were restricted to human leukocyte antigen (HLA). Whether HLA restriction is required for human T-reg cells to ameliorate colitis following LD IL-2 therapy has not been demonstrated. Here, we show that treatment with LD IL-2 reduced 2,4,6-trinitrobenzensulfonic acid (TNBS) colitis severity in NOD.Prkdc(scid)Il2rg(-/-) (NSG) mice reconstituted with human CD34(+) hematopoietic stem cells. These data demonstrate the utility of standard immune humanized NSG mice as a pre-clinical model system to evaluate therapeutics targeting human T-reg cells to treat IBD.
date: 2021-02-24
date_type: published
publication: Frontiers in immunology
volume: 12
publisher: Frontiers
id_number: 10.3389/fimmu.2021.630204
refereed: TRUE
issn: 1664-3224
official_url: https://www.frontiersin.org/articles/10.3389/fimmu.2021.630204/full
citation:   Tyagi, Rajeev K and Jacobse, Justin and Li, Jing and Allaman, Margret M. and Otipoby, Kevin L. and Sampson, Erik R. and Wilson, K T and Goettel, Jeremy A.  (2021) HLA-Restriction of Human Treg Cells Is Not Required for Therapeutic Efficacy of Low-Dose IL-2 in Humanized Mice.  Frontiers in immunology, 12.   ISSN 1664-3224