CD8-positive T lymphocytes specific for murine cytomegalovirus immediate-early antigens mediate protective immunity.
We have shown in a murine model system for acute, lethal cytomegalovirus (CMV) disease in the immunocompromised natural host that control of virus multiplication in tissues, protection from virus-caused tissue destruction, and survival are mediated by virus-specific CD8+ CD4-T lymphocytes. Protection from a lethal course of disease did not result in a rapid establishment of virus latency, but led to a long-lasting, persistent state of infection. The CD8- CD4+ subset of T lymphocytes was not effective by itself in controlling murine CMV (MCMV) multiplication in tissue or essential for the protective function of the CD8+ CD4- effector cells. The antiviral efficacy of the purified CD8+ CD4- subset was not impaired by preincubation with fibroblasts that presented viral structural antigens, but was significantly reduced after depletion of effector cells specific for the nonstructural immediate-early antigens of MCMV, which are specified by the first among a multitude of viral genes expressed during MCMV replication in permissive cells. Thus, MCMV disease provides the first example of a role for nonstructural herpesvirus immediate-early antigens in protective immunity.
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D003001:Cloning, Molecular; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005347:Fibroblasts; D005814:Genes, Viral; D017874:Immediate-Early Proteins; D007108:Immune Tolerance; D007111:Immunity, Cellular; D051379:Mice; D008807:Mice, Inbred BALB C; D009693:Nucleic Acid Hybridization; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*; D014779:Virus Replication
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D000956:Antigens, Viral; D017874:Immediate-Early Proteins; C044582:immediate-early proteins, cytomegalovirus