TY - JOUR
T1 - Th1 and Th17 immunocompetence in humanized NOD/SCID/IL2rγnull mice
AU - Rajesh, Deepika
AU - Zhou, Ying
AU - Jankowska-Gan, Ewa
AU - Roenneburg, Drew Allan
AU - Dart, Melanie L.
AU - Torrealba, Jose
AU - Burlingham, William J.
N1 - Funding Information:
MERC foundation of Madison, Wisconsin (grant number 233HG19 ) awarded to Dr. Burlingham provided the major funding for this research. We also thank Dr. Debra Bloom for performing human BAFF analysis, and Drs. William Weidanz, Jenny Gumperz, Shannon Kenney, Clive Svensen, and Timothy Kamp for their support in the development of the model.
PY - 2010/6
Y1 - 2010/6
N2 - 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.
AB - 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.
KW - Delayed type hypersensitivity
KW - Humanized mice
KW - T-cell response
KW - Th1 and Th17 response
KW - Trans vivo delayed type hypersensitivity
UR - http://www.scopus.com/inward/record.url?scp=77952887847&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77952887847&partnerID=8YFLogxK
U2 - 10.1016/j.humimm.2010.02.019
DO - 10.1016/j.humimm.2010.02.019
M3 - Article
C2 - 20298731
AN - SCOPUS:77952887847
SN - 0198-8859
VL - 71
SP - 551
EP - 559
JO - Human Immunology
JF - Human Immunology
IS - 6
ER -