@article{open2660, volume = {12}, month = {February}, author = {Rajeev K Tyagi and Justin Jacobse and Jing Li and Margret M. Allaman and Kevin L. Otipoby and Erik R. Sampson and K T Wilson and Jeremy A. Goettel}, note = {Open Access}, title = {HLA-Restriction of Human Treg Cells Is Not Required for Therapeutic Efficacy of Low-Dose IL-2 in Humanized Mice}, publisher = {Frontiers}, journal = {Frontiers in immunology}, year = {2021}, keywords = { IBD; IL-2; Tregs; colitis; humanized.}, url = {http://crdd.osdd.net/open/2660/}, 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.} }