Cytolysis of Junin infected target cells by immune guinea pig spleen cells

Abstract

Spleen cells from guinea pigs infected with an attenuated strain of Junin virus (the causative agent of Argentine hemorrhagic fever) specifically lysed virus-infected syngeneic target cells in vitro. This activity was detected as early as 6 days after infection, reached a maximum on days 10-13, and persisted at lower levels, at least through day 30. Monoclonal antibody to guinea pig T cells had no effect on the activity. After B or T cell enrichment techniques, the cytolysis was found with the B cell fraction. Aggregated IgG blocked the cytolysis. These characteristics suggested lytic activity was mediated at least in part by an antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism. Although some cytolysis could be detected by using exogenously added antiserum and normal spleen effector cells, such reconstruction showed less efficient killing than when spleen cells from Junin-infected guinea pigs were used. This apparent discrepancy was resolved when spleen cells from these infected animals exhibited enhanced activity in non-viral ADCC systems as well. The cytotoxic activity by spleen cells against Junin-infected targets was detected only with non-fatal Junin infections. Cytolysis could not be measured in spleen cell suspensions from guinea pigs lethally infected with Junin virus; i.e. adults infected with a virulent strain of Junin and baby guinea pigs or immunosuppressed adult animals infected with an attenuated strain. However, spleen cells from both the immunosuppressed, infected adults and the adult guinea pigs infected with a virulent strain of Junin were able to mediate cytotoxicity in a nonviral system (antibody-sensitized Vero cells). The development of spleen cell cytotoxicity by Junin-infected guinea pigs against Junin-infected target cells correlated with whether the infection was resolved or was lethal.