title: IL-2 receptor γ-chain molecule is critical for intestinal T-cell reconstitution in humanized mice.
abstract: Intestinal immune cells are important in host defense, yet the determinants for human lymphoid homeostasis in the intestines are poorly understood. In contrast, lymphoid homeostasis has been studied extensively in mice, where the requirement for a functional common γ-chain molecule has been established. We hypothesized that humanized mice could offer insights into human intestinal lymphoid homeostasis if generated in a strain with an intact mouse common γ-chain molecule. To address this hypothesis, we used three mouse strains (non-obese diabetic (NOD)/severe-combined immunodeficient (SCID) (N/S); NOD/SCID γ-chain(-/-) (NSG); and Rag2(-/-) γ-chain(-/-) (DKO)) and two humanization techniques (bone marrow liver thymus (BLT) and human CD34(+) cell bone marrow transplant of newborn mice (hu)) to generate four common types of humanized mice: N/S-BLT, NSG-BLT, NSG-hu, and DKO-hu mice. The highest levels of intestinal human T cells throughout the small and large intestines were observed in N/S-BLT mice, which have an intact common γ-chain molecule. Furthermore, the small intestine lamina propria T-cell populations of N/S-BLT mice exhibit a human intestine-specific surface phenotype. Thus, the extensive intestinal immune reconstitution of N/S-BLT mice was both quantitatively and qualitatively better when compared with the other models tested such that N/S-BLT mice are well suited for the analysis of human intestinal lymphocyte trafficking and human-specific diseases affecting the intestines.
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, UNC Center for AIDS Research, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
authors.forename: P W
authors.initials: PW
authors.lastname: Denton
authors.forename: T
authors.initials: T
authors.lastname: Nochi
authors.forename: A
authors.initials: A
authors.lastname: Lim
authors.forename: J F
authors.initials: JF
authors.lastname: Krisko
authors.forename: F
authors.initials: F
authors.lastname: Martinez-Torres
authors.forename: S K
authors.initials: SK
authors.lastname: Choudhary
authors.forename: A
authors.initials: A
authors.lastname: Wahl
authors.forename: R
authors.initials: R
authors.lastname: Olesen
authors.forename: W
authors.initials: W
authors.lastname: Zou
authors.forename: J P
authors.initials: JP
authors.lastname: Di Santo
authors.forename: D M
authors.initials: DM
authors.lastname: Margolis
authors.forename: J V
authors.initials: JV
authors.lastname: Garcia
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology*; D016026:Bone Marrow Transplantation; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D006706:Homeostasis; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics / Q000378:metabolism*; D007422:Intestines / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000276:immunology*; D018183:Transplantation Chimera
chemical_list: D018952:Antigens, CD34; D004268:DNA-Binding Proteins; D053631:Interleukin Receptor Common gamma Subunit; C499308:Rag2 protein, mouse