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 n eutralization of gamma interferon with monoclonal antibodies, indicating an important role for this pleiotropic cytokine, Here, we demonstrate that mo use gamma interferon has no direct antiviral effect in vitro and in vivo, T he breakdown of resistance is due neither to a switch in the T-helper respo nse nor to an impaired migration of CD4(+) T cells. Neutralization of gamma interferon interferes with the major histocompatibility complex class II-d ependent antigen presentation and subsequent proliferation of CD4(+) T cell s 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.