PROTECTION AGAINST LETHAL INFLUENZA-VIRUS ENCEPHALITIS BY INTRANASALLY PRIMED CD8(-CELLS() MEMORY T)

The neurotropic influenza virus strain A/WSN (H1N1) caused a rapidly f atal encephalitis after intracerebral inoculation into naive mice, Int ranasal immunization with the same virus (homotypic) completely protec ted mice against a subsequent intracerebral challenge with A/WSN; ther e 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 we re 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 immu nization with the heterotypic influenza strain A/X31 (H3N2) did not ge nerate protective Ab, but despite an acute illness, 80% of mice surviv ed the subsequent intracerebral challenge, Immune protection was assoc iated with CD8(+) T cell infiltration throughout the brain substance, together with widespread up-regulation of intracerebral MHC class I an d MHC class II expression. In vivo T cell subset depletion showed that heterotypic protection was dependent upon CD8(+), but not CD4(+), T c ells, This model system demonstrates some of the mechanisms through wh ich the immunity generated by an initial extracerebral virus infection may protect against later intracerebral virus replication.