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

Heemskerk, Mirjam H. M.; Schilham, Marco W.; Schoemaker, Henriette M.; Spierenburg, Gerrit; Spaan, Willy J. M.; Boog, Claire J. P.

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.