Th1 and Th17 immunocompetence in humanized NOD/SCID/IL2rγnull mice

Deepika Rajesh, Ying Zhou, Ewa Jankowska-Gan, Drew Allan Roenneburg, Melanie L. Dart, Jose Torrealba, William J. Burlingham

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56 Scopus citations

Abstract

We evaluated the immunocompetence of human T cells in humanized NOD-SCID interleukin (IL)-2r-γ-null (hu-NSG) mice bearing a human thymic organoid, after multilineage reconstitution with isogeneic human leukocytes. Delayed type hypersensitivity (DTH) response was assessed by a direct footpad challenge of the immunized hu-NSG host, or by transfer of splenocytes from immunized hu-NSG, along with antigen, into footpads of C.B-17 scid mice (trans vivo [tv] DTH). Both methods revealed cellular immunity to tetanus toxoid (TT) or collagen type V (ColV). Immunohistochemical analysis of the swollen footpads revealed infiltration of human CD45+ cells, including CD3+ T cells, CD68+ macrophages, and murine Ly6G+ neutrophils. We observed a significant correlation between the percentage of circulating human CD4+ cells and the direct DTH swelling response to TT. The tvDTH response to TT was inhibited by anti-interferon-γ, whereas the tvDTH response to collagen V was inhibited by anti-IL-17 antibody, mimicking the cytokine bias of adult human T cells to these antigens. hu-NSG mice were also capable of mounting a B-cell response (primarily IgM) to TT antigen. The activation of either Th1- or Th17-dependent cellular immune response supports the utility of hu-NSG mice as a surrogate model of allograft rejection and autoimmunity.

Original languageEnglish (US)
Pages (from-to)551-559
Number of pages9
JournalHuman Immunology
Volume71
Issue number6
DOIs
StatePublished - Jun 1 2010

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Keywords

  • Delayed type hypersensitivity
  • Humanized mice
  • T-cell response
  • Th1 and Th17 response
  • Trans vivo delayed type hypersensitivity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Rajesh, D., Zhou, Y., Jankowska-Gan, E., Roenneburg, D. A., Dart, M. L., Torrealba, J., & Burlingham, W. J. (2010). Th1 and Th17 immunocompetence in humanized NOD/SCID/IL2rγnull mice. Human Immunology, 71(6), 551-559. https://doi.org/10.1016/j.humimm.2010.02.019