Beta 2-microglobulin-deficient mice demonstrate class II MHC restricted anti-viral CD4+ but not CD8+ CTL against influenza-sensitized autologous splenocytes.

ABSTRACT

Mice transgenic for beta 2-microglobulin gene deletion (beta 2M-/-) 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 2M deficient cells by allogeneic mice and rejection of MHC-incompatible tumor cells by beta 2M-/- mice. After influenza inoculation, we found no evidence for anti-influenza CD8 CTL activity from the lungs or spleens of beta 2M-/- 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 2M-/- 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 2M-/- 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 2M-/- mice. Development of anti-tumor CTLs and anti-viral CTLs may arise via different mechanisms.