HLA-Restriction of Human Treg Cells Is Not Required for Therapeutic Efficacy of Low-Dose IL-2 in Humanized Mice

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

Full text not available from this repository. (Request a copy)
Official URL: https://www.frontiersin.org/articles/10.3389/fimmu...

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.

Item Type: Article
Additional Information: Open Access
Uncontrolled Keywords: IBD; IL-2; Tregs; colitis; humanized.
Subjects: Q Science > QR Microbiology > QR180 Immunology
Depositing User: Dr. K.P.S.Sengar
Date Deposited: 26 Mar 2021 04:19
Last Modified: 26 Mar 2021 04:19
URI: http://crdd.osdd.net/open/id/eprint/2660

Actions (login required)

View Item View Item