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

Institute of Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, 97078 Würzburg, Germany¹
Institute of Pathology, University of Würzburg, Würzburg, Germany²
Centre for Peptide and Protein Engineering, Queen’s University of Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK³

Author for correspondence: Stefan Niewiesk. Fax +49 931 201 3934. e-mail niewiesk{at}vim.uni-wuerzburg.de

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-dxk, 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^d-restricted CD8⁺ T cells, which are highly lytic in vitro after transfer, protect naive animals against MV-induced encephalitis (MVE). In contrast, K^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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