Lymphocytic choriomeningitis virus-induced immunosuppression: a virus-induced macrophage defect

Abstract

Primary immunizing infections with LCM virus result in a transient depression of the in vitro proliferative responses of splenic lymphocytes to mitogens specifically reactive with T cells or B cells. This depression of lymphocyte function is the result of a virus-induced defect in an adherent, phagocytic cell population required for in vitro lymphocyte activation. Depressed responses persist for about 1 week after virus clearance and can be corrected by the addition of normal PEM or 2-ME to infected spleen cell cultures. Although the precise nature of this defect remains unclear, it is postulated that it is due to a productive infection of macrophages and their precursors that renders them dysfunctional. Secondary LCM virus infections do not result in depressed in vitro responses to mitogens, presumably because of rapid virus clearance and limited numbers of infected cells. Primary infections of immunologically immature mice, mice rendered functionally athymic, or mice treated with nonspecific immunosuppressive agents result in LCM virus persistence. Shortly after infection, these animals show a similar depression of immunologic reactivity that returns to normal as the virus carrier state becomes established. Despite virus persistence, few PEM from established LCM virus carrier mice contain viral antigens and these cells function normally. Thus, LCM virus-induced immunosuppression appears to reflect a subtle cytopathic effect of LCM virus replication that is not mediated by the virus-specific cell-mediated immune mechanisms responsible for acute LCM virus disease.