Protection against lethal influenza virus encephalitis by intranasally primed CD8+ memory T cells.
The neurotropic influenza virus strain A/WSN (H1N1) caused a rapidly fatal encephalitis after intracerebral inoculation into naive mice. Intranasal immunization with the same virus (homotypic) completely protected mice against a subsequent intracerebral challenge with A/WSN; there was no clinical disease, and infectious virus could not be recovered from the brain. In vivo depletion of CD4+ or CD8+ T cell subsets did not affect homotypic protection, and the pups of immune mothers were also protected against a lethal intracerebral challenge with A/WSN, suggesting that the Ab produced by intranasal priming was sufficient to protect mice against later intracerebral infection. Intranasal immunization with the heterotypic influenza strain A/X31 (H3N2) did not generate protective Ab, but despite an acute illness, 80% of mice survived the subsequent intracerebral challenge. Immune protection was associated with CD8+ T cell infiltration throughout the brain substance, together with widespread up-regulation of intracerebral MHC class I and MHC class II expression. In vivo T cell subset depletion showed that heterotypic protection was dependent upon CD8+, but not CD4+, T cells. This model system demonstrates some of the mechanisms through which the immunity generated by an initial extracerebral virus infection may protect against later intracerebral virus replication.
Stevenson
P G
PG
Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
Hawke
S
S
Bangham
C R
CR
D000208:Acute Disease; D000281:Administration, Intranasal; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000096:biosynthesis; D001921:Brain / Q000821:virology; D018792:Encephalitis, Viral / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D007112:Immunity, Maternally-Acquired; D007156:Immunologic Memory; D009980:Influenza A virus / Q000145:classification / Q000276:immunology* / Q000302:isolation & purification; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007267:Injections; D008212:Lymphocyte Depletion; D008223:Lymphoma / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014611:Vaccination
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D007252:Influenza Vaccines