Activation of virus-specific major histocompatibility complex class II-restricted CD8+ cytotoxic T cells in CD4-deficient mice

Acute enteritic or respiratory disease is a consequence of coronavirus infection in man and rodents. Mouse hepatitis virus, stain A59 (MHV-A59) causes acute hepatitis in mice and rats and induces a response of major histocompatibility complex (MHC) class II-restricted CD4⁺ cytotoxic T cells, protecting mice against acute infection. In the present study we show that MHV-A59 infection of mice that lack a functional CD4 gene activates effector cells of the CD8⁺ phenotype. These cytotoxic T cells lyse virus-infected target cells in a MHC class II-restricted fashion. The results indicate that CD8⁺ T cells have the potential to utilize MHC class II as restriction element, illustrating that the immune system can effectively deal with evading microorganisms, such as viruses which down-regulate MHC class I.