Open AccessHuman T-cell-mediated destruction of allogeneic dermal microvessels in a severe combined immunodeficient mouse.
Author(s) -
Allan G. Murray,
Peter Petzelbauer,
Christopher C.W. Hughes,
José Luís Costa,
Philip W. Askenase,
Jordan S. Pober
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.19.9146
Subject(s) - human skin , cd8 , cytolysis , perforin , cell adhesion molecule , major histocompatibility complex , biology , humanized mouse , immunology , t cell , chimera (genetics) , histocompatibility , human leukocyte antigen , pathology , medicine , antigen , cytotoxic t cell , immune system , in vitro , gene , biochemistry , genetics
We developed a chimeric human-severe combined immunodeficient mouse model to study human allograft rejection. Mice received first partial thickness human skin grafts and then, after anastomosis of the mouse with graft human microvessels, human lymphocytes allogeneic to the skin. By 2 weeks, the skin grafts uniformly developed changes that resemble first-set skin rejection in humans. Vascular cell adhesion molecule 1 and major histocompatibility complex class II molecules were induced on the human vascular endothelium at day 6, prior to significant T-cell infiltration. Perivascular human CD4+ and CD8+ T-cell infiltrates were marked by day 11. Some T cells, adjacent to injured human vessels, expressed the cytolytic granule protein perforin. The human microvessels were destroyed by day 16 without significant damage to human keratinocytes or adjacent mouse microvessels. This small animal model may permit evaluation of potential therapeutic reagents that inhibit human T-cell-mediated injury.