Inhibition of major histocompatibility complex class II-dependent antigen presentation by neutralization of gamma interferon leads to breakdown of resistance against measles virus-induced encephalitis.
BALB/c mice are resistant to measles virus (MV)-induced encephalitis due to their strong MV-specific CD4(+) T-cell response. Resistance is broken by neutralization of gamma interferon with monoclonal antibodies, indicating an important role for this pleiotropic cytokine. Here, we demonstrate that mouse gamma interferon has no direct antiviral effect in vitro and in vivo. The breakdown of resistance is due neither to a switch in the T-helper response nor to an impaired migration of CD4(+) T cells. Neutralization of gamma interferon interferes with the major histocompatibility complex class II-dependent antigen presentation and subsequent proliferation of CD4(+) T cells in vitro and in vivo. In consequence, the reduction in numbers of CD4(+) T cells below a protective threshold leads to susceptibility to MV-induced encephalitis.
Institute of Virology and Immunobiology, University of Wuerzburg, 97078 Wuerzburg, Germany.
G
G
Weidinger
G
G
Henning
V
V
ter Meulen
S
S
Niewiesk
D000818:Animals; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D018792:Encephalitis, Viral / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology*; D008213:Lymphocyte Activation; D008457:Measles / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma