Characterization of Theiler's murine encephalomyelitis virus (TMEV)-specific delayed-type hypersensitivity responses in TMEV-induced demyelinating disease: correlation with clinical signs.
After intracerebral inoculation of Theiler's murine encephalomyelitis virus (TMEV), certain mouse strains develop a persistent central nervous system (CNS) infection and inflammatory demyelinating lesions containing infiltrates of mononuclear cells and macrophages. Previous findings demonstrating a strong correlation between disease incidence, the presence of particular H-2 region genotypes, and development of high levels of TMEV-specific delayed-type hypersensitivity (DTH) supported an immune-mediated basis for myelin breakdown. These findings led us to examine whether a possible causal relationship would be supported by a temporal analysis comparing the onset of clinical disease and the development of TMEV-specific cellular or humoral immune responses in susceptible and resistant strains. In susceptible SJL/J mice, TMEV-specific DTH and T cell proliferative (Tprlf) responses developed within 10 to 14 days postinfection, preceded the onset of clinical signs, and remained elevated for 6 mo. In contrast, resistant BALB/c mice developed low levels of TMEV-specific Tprlf and no measurable DTH. However, both strains attained comparable levels of TMEV-specific serum antibody responses with parallel kinetics. Both DTH and Tprlf responses in susceptible SJL/J mice were shown to be specific for TMEV and mediated by L3T4+, Lyt-1+2-, class II-restricted T cells. A model is proposed implicating an effector role for TMEV-specific DTH, wherein lymphokine release by virus-specific DTH T cells leads to the recruitment, accumulation, and activation of macrophages in CNS tissue, which cause bystander myelin destruction and provide a permissive population of host cells for TMEV persistence.
R J
RJ
Clatch
H L
HL
Lipton
S D
SD
Miller
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D000954:Antigens, Surface / Q000032:analysis; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology; D001667:Binding, Competitive; D003711:Demyelinating Diseases / Q000276:immunology* / Q000382:microbiology; D004770:Enterovirus / Q000276:immunology*; D004769:Enterovirus Infections / Q000276:immunology* / Q000382:microbiology; D000939:Epitopes / Q000276:immunology; D006183:H-2 Antigens / Q000008:administration & dosage / Q000235:genetics; D006968:Hypersensitivity, Delayed / Q000276:immunology* / Q000382:microbiology; D007116:Immunization, Passive; D008213:Lymphocyte Activation; D004680:Maus Elberfeld virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000637:transplantation; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000956:Antigens, Viral; D000939:Epitopes; D006183:H-2 Antigens