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-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.
Weidinger
Gerald
G
Institute of Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, 97078 Würzburg, Germany1.
Czub
Stefanie
S
Institute of Pathology, University of Würzburg, Würzburg, Germany2.
Neumeister
Claudia
C
Institute of Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, 97078 Würzburg, Germany1.
Harriott
Pat
P
Centre for Peptide and Protein Engineering, Queen's University of Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK3.
Ter Meulen
Volker
V
Institute of Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, 97078 Würzburg, Germany1.
Niewiesk
Stefan
S
Institute of Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, 97078 Würzburg, Germany1.
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018792:Encephalitis, Viral / Q000276:immunology*; D007111:Immunity, Cellular; D008211:Lymphocyte Cooperation; D008457:Measles / Q000276:immunology*; D008459:Measles virus; D051379:Mice; D008807:Mice, Inbred BALB C