Role of CD4(+) and CD8(+) T cells in the prevention of measles virus-induced encephalitis in mice

Depending on their major histocompatibility complex (MHC) haplotype, inbred mouse strains are either resistant (H2-d, BALB/c), susceptible (H2-k, C3H) or partially resistant (H2-d x k, BaCF1) to intracerebral infection with t he neurotropic rodent-adapted measles virus (MV) strain CAM/RBH, Here, mort ality is demonstrated to be correlated directly with virus spread and virus replication in the CNS and to be inversely correlated with the activation of MV-specific T cells, Previously, it has been shown that primary CD4(+) T cells alone are protective in the resistant background. In the susceptible background, CD4(+) T cells acquire protective capacity after immunization with a newly defined CD4(+) T cell epitope peptide. In the partially resist ant mice, CD4(+) T cells provide help for CD8(+) T cells and protect in coo peration with them. It seems that the lyric capacity of CD8(+) T cells is c rucial in providing protection, as MV-specific L-d-restricted CD8(+) T cell s, which are highly lytic in vitro after transfer, protect naive animals ag ainst MV-induced encephalitis (MVE), In contrast, K-k-restricted CD8(+) T c ells with low lytic capacity do not protect, In the MVE model, CD4(+) T cel ls are able to protect either alone (resistant mice), through cooperation w ith CD8(+) T cells (intermediate susceptible) or after immunization as seco ndary T cells (susceptible mice). CD8(+) T cells are able to protect alone after immunization if they are cytolytic, Thus, susceptibility and resistan ce depend upon the functional composition of CD4(+) and CD8(+) T cells gove rned by the MHC haplotype.