Macrophage migration inhibition as a correlate of cell-mediated immunity to herpes simplex virus type 2 in mice

Mice inoculated intraperitoneally or intravenously with herpes simplex virus type 2 (HSV-2) develop a focal necrotizing hepatitis. The livers show expanding foci of necrosis and increasing virus content during the first days of the infection with maximal titers achieved on day 3. The clearance of virus from the organ is manifest from day 4 onward with the most dramatic fall in virus content occurring between days 4 and 5. The development of immunity during the course of infection was assessed by adoptive transfer experiments and by measuring macrophage migration inhibition factor (MIF) production of spleen cells in an indirect agarose microdroplet assay. Antiviral activity of adoptively transferred spleen cells was demonstrable from day 4 of the infection when 50 X 10(6) spleen cells were transferred into recipient mice infected 24 h previously. MIF production in spleen cell cultures stimulated with antigen was found to be specific in that activity was only detected in cultures derived from immune mice and stimulated with the virus antigen. The response was found to be antigen-dose and cell-number dependent. Significant MIF production was demonstrable in spleen cell cultures derived from mice 3 days after the infection, i.e. concomitant with the initiation of recovery and before antiviral activity can be detected in transfer experiments. It is suggested that a delayed type hypersensitivity reaction with lymphokine production leading to recruitment of macrophages and their retention and activation in the foci of infection may be a major factor in the recovery from the infection.