Perforin-Dependent Cytolytic Responses in β2-Microglobulin-Deficient Mice

The ability of β2-microglobulin-deficient mice (B6.β2μo) mice to reject syngeneic and major histocompatability (MHC) class I-deficient tumor grafts was examined with a view to determining residual cytotoxic activities that exist in these mice. In particular, the cytotoxic activities of NK cells and CD8+ cytotoxic T lymphocytes (CTL) reactive against self-MHC class I were assessed using a variety of gene-targeted mice. The creation of mice doubly deficient for perforin and β2μ (B6.Po.β2μo) enabled the determination that perforin was responsible for the cytotoxic activity of NK cells and CD8+ CTL reactive against self-MHC class I. Dependence on perforin function was demonstrated for the cytotoxicity of these effectors in vitro and for the ability of these effectors to reject a variety of tumors in vivo.