BETA(2)-MICROGLOBULIN-DEFICIENT MICE DEMONSTRATE CLASS-II MHC RESTRICTED ANTIVIRAL CD4(+) BUT NOT CD8(+) CTL AGAINST INFLUENZA-SENSITIZED AUTOLOGOUS SPLENOCYTES

Mice transgenic for beta(2)-microglobulin gene deletion (beta(2)M(-/-)) can clear respiratory pathogens but at a slower rate than control mice. How these mice eliminate virus is not known, but the process is believed to involve CD4(+) T cells. Recent studies from other laboratories have suggested a role for CD8(+) cytotoxic T lymphocytes (CTLs) in both recognition of beta(2)M deficient cells by allogeneic mice and rejection of MHC-incompatible tumor cells by beta(2)M(-/-) mice. After influenza inoculation, we found no evidence for anti-influenza CD8 CTL activity from the lungs or spleens of beta(2)M(-/-) mice. Anti-influenza CD4(+), class-II restricted CTL activity was demonstrated from both the lungs and spleens. We next used mitogen-stimulated splenocytes from beta(2)M(-/-) mice for targets in an in vitro CTL assay. This method for determining MHC class II CTL activity showed that the lungs and spleens of influenza-infected beta(2)M(-/-) mice contained precursors to CD4(+), but not CD8(+), effector CTLs. The data indicate that CD8(+) CTLs have no role in anti-viral activity in beta(2)M(-/-) mice. Development of anti-tumor CTLs and anti-viral CTLs may arise via different mechanisms.