Keith Wilson
Faculty Member
Last active: 3/17/2021

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

Tyagi RK, Jacobse J, Li J, Allaman MM, Otipoby KL, Sampson ER, Wilson KT, Goettel JA
Front Immunol. 2021 12: 630204

PMID: 33717161 · PMCID: PMC7945590 · DOI:10.3389/fimmu.2021.630204

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

Copyright © 2021 Tyagi, Jacobse, Li, Allaman, Otipoby, Sampson, Wilson and Goettel.

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