IL-2 receptor γ-chain molecule is critical for intestinal T-cell reconstitution in humanized mice.

Mucosal Immunology
Paul W DentonJ Victor Garcia

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 ...Continue Reading

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Citations

Oct 30, 2013·The Journal of Infectious Diseases·Michael A BrehmDale L Greiner
Jan 15, 2014·PLoS Pathogens·Paul W DentonJ Victor Garcia
Mar 13, 2014·Journal of Immunological Methods·Michael A BrehmLeonard D Shultz
Jun 22, 2014·Journal of Immunological Methods·Angela Wahl, J Victor Garcia
Jan 22, 2013·Annual Review of Immunology·Anthony RongvauxMarkus G Manz
Feb 2, 2016·The Journal of Clinical Investigation·J Victor Garcia
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Jun 26, 2013·Cell Reports·Tomonori NochiJ Victor Garcia
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Oct 2, 2014·PloS One·Francisco Martinez-TorresPaul W Denton
Oct 4, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gaël Moquin-BeaudryChristian Beauséjour
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May 1, 2021·Viruses·Kazutaka TeraharaYasuko Tsunetsugu-Yokota
Apr 7, 2019·Microbiology Spectrum·Yan Li, James P Di Santo

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