Human delayed-type hypersensitivity reaction in a SCID mouse engrafted with human T cells and autologous skin.
We have developed and animal model to study human delayed-type hypersensitivity reactions occurring in a human environment within a mouse host. Human skin was grafted onto the backs and autologous human immune cells were injected into the peritoneal cavity of mice with severe combined immunodeficiency. Seven and 14 d after grafting, 2-50% of total white blood and spleen cells were of human origin. Mouse spleen-derived human T cells from tetanus toxoid-sensitized donors proliferated in response to tetanus toxoid as measured by [3H]thymidine uptake, and the strength of this proliferative response equaled that with pre-graft T cells from the same donor. Proliferation was blocked with monoclonal antibodies to human but not to mouse major histocompatibility complex antigens and with anti-human CD4 monoclonal antibodies. In vivo vaccination of mice with tetanus toxoid did not enhance proliferation of mouse spleen-derived human T cells in response to antigen. Injection of tetanus toxoid into the human skin graft caused a perivascular human CD4+/CD25+ T-cell infiltrate, which was not present when tetanus toxoid was injected into adjacent mouse skin. We conclude that human T cells grafted into mice with severe combined immunodeficiency retain their function, that human T cells specifically recognize human but not mouse skin as homing sites, and that human T-cell responses depend on the human micro-environment. This model lends itself to studies of endothelium-T-cell interactions, T-cell activation within skin, and chronic inflammatory skin diseases.
Petzelbauer
P
P
Department of Dermatology, University of Vienna Medical School, Austria.
Gröger
M
M
Kunstfeld
R
R
Petzelbauer
E
E
Wolff
K
K
D000818:Animals; D001773:Blood Cells / Q000166:cytology; D000939:Epitopes; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007962:Leukocytes / Q000166:cytology; D051379:Mice; D016513:Mice, SCID; D016038:Skin Transplantation; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000637:transplantation*; D013745:Tetanus Toxoid / Q000494:pharmacology; D014182:Transplantation, Autologous
D000939:Epitopes; D013745:Tetanus Toxoid