We tried to establish an experimental animal model for studies of possible organ-specific antiviral mechanisms. An intratracheal inoculation with murine cytomegalovirus proceeded asynchronously to acute infection of multiple organs with respect to time course of virus load in organs. This result already anticipates the existence of organ difference in antiviral defense mechanism. We depleted systemically each of the major T-cell subsets in the infected mice by administration of specific monoclonal antibody to see whether different organs respond similarly or differently to the depletion. The depletion of CD4+ T cells starting prior to virus inoculation resulted in an increase in virus load relative to the untreated control in all the 5 organs examined, i.e. the spleen (regarding as the organ representing systemic response), lungs, kidneys, the liver and salivary glands, but with a different kinetics each other. When the depletion of CD8+ T cells started before infection, on the other hand, the organs responded in one of three different ways to the depletion: an increase in virus load relative to the untreated control in the spleen, lungs and kidneys with a kinetics different from each other; only a small increase in virus load in the liver; and no increase in virus load in salivary glands. When the depletion of CD8+ T cells started at 11 days after infection, the spleen, lungs and kidneys, in which virus load increased upon the depletion of CD8+ T cells starting prior to infection, were further found to respond in one of two ways to the depletion: an increase in virus load detectable within three days in the spleen and kidneys, and increase not detectable up to 14 days after depletion in lungs. We conclude that defense against virus operates differently among organs in the body in acute infection of multiple organs following an intratracheal inoculation with murine cytomegalovirus. This model should offer an opportunity to study local mechanisms of defense against viral infection.
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