Beta 2-microglobulin-deficient mice demonstrate class II MHC restricted anti-viral CD4+ but not CD8+ CTL against influenza-sensitized autologous splenocytes.
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.
Taylor
S F
SF
Department of Veterans Affairs Medical Center, University of Florida College of Medicine, Gainesville 32608, USA.
Bender
B S
BS
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D003602:Cytotoxicity, Immunologic; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D016130:Immunophenotyping; D008168:Lung / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D009975:Orthomyxoviridae / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000821:virology*; D001613:beta 2-Microglobulin / Q000172:deficiency* / Q000235:genetics
D000949:Histocompatibility Antigens Class II; D001613:beta 2-Microglobulin