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

oleh: Rajeev K. Tyagi, Justin Jacobse, Justin Jacobse, Jing Li, Margret M. Allaman, Kevin L. Otipoby, Erik R. Sampson, Keith T. Wilson, Keith T. Wilson, Keith T. Wilson, Keith T. Wilson, Keith T. Wilson, Keith T. Wilson, Jeremy A. Goettel, Jeremy A. Goettel, Jeremy A. Goettel, Jeremy A. Goettel, Jeremy A. Goettel

Format: Article
Diterbitkan: Frontiers Media S.A. 2021-02-01

Deskripsi

Regulatory T (Treg) cells are essential to maintain immune homeostasis in the intestine and Treg 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 Treg 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 Treg 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.PrkdcscidIl2rg-/- (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 Treg cells to treat IBD.