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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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 2010

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Immunocompetence
SCID Mice
Tetanus Toxoid
Delayed Hypersensitivity
T-Lymphocytes
Antigens
Cellular Immunity
Organoids
Collagen Type V
Interleukin-17
Interleukins
Autoimmunity
Interferons
Allografts
Immunoglobulin M
Neutrophils
Leukocytes
B-Lymphocytes
Collagen
Macrophages

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Medicine(all)

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

Th1 and Th17 immunocompetence in humanized NOD/SCID/IL2rγnull mice. / Rajesh, Deepika; Zhou, Ying; Jankowska-Gan, Ewa; Roenneburg, Drew Allan; Dart, Melanie L.; Torrealba, Jose; Burlingham, William J.

In: Human Immunology, Vol. 71, No. 6, 06.2010, p. 551-559.

Research output: Contribution to journalArticle

Rajesh, D, Zhou, Y, Jankowska-Gan, E, Roenneburg, DA, Dart, ML, Torrealba, J & Burlingham, WJ 2010, 'Th1 and Th17 immunocompetence in humanized NOD/SCID/IL2rγnull mice', Human Immunology, vol. 71, no. 6, pp. 551-559. https://doi.org/10.1016/j.humimm.2010.02.019
Rajesh, Deepika ; Zhou, Ying ; Jankowska-Gan, Ewa ; Roenneburg, Drew Allan ; Dart, Melanie L. ; Torrealba, Jose ; Burlingham, William J. / Th1 and Th17 immunocompetence in humanized NOD/SCID/IL2rγnull mice. In: Human Immunology. 2010 ; Vol. 71, No. 6. pp. 551-559.
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