Organ-dependent T-cell subset requirement in defense against virus in miceacutely and systemically infected with murine cytomegalovirus

We tried to establish an experimental animal model for studies of possible organ-specific antiviral mechanisms. An intratracheal inoculation with muri ne cytomegalovirus proceeded asynchronously to acute infection of multiple organs with respect to time course of virus load in organs. This result alr eady anticipates the existence of organ difference in antiviral defense mec hanism. We depleted systemically each of the major T-cell subsets in the in fected mice by administration of specific monoclonal antibody to see whethe r different organs respond similarly or differently to the depletion. The d epletion 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 or gans examined, i.e. the spleen (regarding as the organ representing systemi c response), lungs, kidneys, the liver and salivary glands, but with a diff erent kinetics each other. When the depletion of CD8(+) T cells started bef ore infection, on the other hand, the organs responded in one of three diff erent ways to the depletion: an increase in virus load relative to the untr eated control in the spleen, lungs and kidneys with a kinetics different fr om each other; only a smalt increase in virus load in the liver; and no inc rease in virus load in salivary glands. When the depletion of CD8(+) T cell s started at 11 days after infection, the spleen, lungs and kidneys, in whi ch 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 depl etion: 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 or gans in the body in acute infection of multiple organs following an intratr acheal inoculation with murine cytomegalovirus. This model should offer an opportunity to study local mechanisms of defense against viral infection.