1887

Abstract

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×k, BaCF1) to intracerebral infection with the neurotropic rodent-adapted measles virus (MV) strain CAM/RBH. Here, mortality 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 resistant mice, CD4 T cells provide help for CD8 T cells and protect in cooperation with them. It seems that the lytic capacity of CD8 T cells is crucial in providing protection, as MV-specific L-restricted CD8 T cells, which are highly lytic after transfer, protect naive animals against MV-induced encephalitis (MVE). In contrast, K-restricted CD8 T cells with low lytic capacity do not protect. In the MVE model, CD4 T cells are able to protect either alone (resistant mice), through cooperation with CD8 T cells (intermediate susceptible) or after immunization as secondary T cells (susceptible mice). CD8 T cells are able to protect alone after immunization if they are cytolytic. Thus, susceptibility and resistance depend upon the functional composition of CD4 and CD8 T cells governed by the MHC haplotype.

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2000-11-01
2020-07-02
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