HLA-Restriction of Human Treg Cells Is Not Required for Therapeutic Efficacy of Low-Dose IL-2 in Humanized Mice
Rajeev K. Tyagi, Justin Jacobse, Jing Li, Margaret M. Allaman, Kevin L. Otipoby, Erik R. Sampson, Keith T. Wilson, Jeremy A. Goettel
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.