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

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

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.630204

DOI=10.3389/fimmu.2021.630204

ISSN=1664-3224

ABSTRACT=<p>Regulatory T (T<sub>reg</sub>) cells are essential to maintain immune homeostasis in the intestine and T<sub>reg</sub> 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<sub>reg</sub> 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<sup>+</sup> T cells were restricted to human leukocyte antigen (HLA). Whether HLA restriction is required for human T<sub>reg</sub> 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.<italic>Prkdc<sup>scid</sup>Il2rg<sup>-/-</sup></italic> (NSG) mice reconstituted with human CD34<sup>+</sup> 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<sub>reg</sub> cells to treat IBD.</p>