Human delayed-type hypersensitivity reaction in a SCID mouse engrafted with human T cells and autologous skin

We have developed an 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 toroid as measured by [H-3]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 toroid did not enhance proliferation of mouse spleen-derived human T cells in response to antigen. Injection of tetanus toroid into the human skin graft caused a perivascular human CD4(+)/CD25(+) T-cell infiltrate, which was not present when tetanus toroid 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 microenvironment. This model lends itself to studies of endothelium-T-cell interactions, T-cell activation within skin, and chronic inflammatory skin diseases.