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

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title HLA-Restriction of Human Treg Cells Is Not Required for Therapeutic Efficacy of Low-Dose IL-2 in Humanized Mice
 
Creator Tyagi, Rajeev K
Jacobse, Justin
Li, Jing
Allaman, Margret M.
Otipoby, Kevin L.
Sampson, Erik R.
Wilson, K T
Goettel, Jeremy A.
 
Subject QR180 Immunology
 
Description 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.
 
Publisher Frontiers
 
Date 2021-02-24
 
Type Article
PeerReviewed
 
Relation https://www.frontiersin.org/articles/10.3389/fimmu.2021.630204/full
http://crdd.osdd.net/open/2660/
 
Identifier Tyagi, Rajeev K and Jacobse, Justin and Li, Jing and Allaman, Margret M. and Otipoby, Kevin L. and Sampson, Erik R. and Wilson, K T and Goettel, Jeremy A. (2021) HLA-Restriction of Human Treg Cells Is Not Required for Therapeutic Efficacy of Low-Dose IL-2 in Humanized Mice. Frontiers in immunology, 12. ISSN 1664-3224