The inflammatory macrophage response to murine cytomegalovirus in genetically susceptible mice

Adherent suppressor cells have often been implicated in the depression of immunocompetence following CMV infections. We have reported that high levels of cytostatic macrophages in the peritoneal cavities of infected mice correlate with genetically-based sensitivity to CMV disease, suggesting they may modulate protective immune responses. This study investigates the properties and kinetics of such cells. Genetically-susceptible BALB/c mice infected with MCMV accumulated activated peritoneal macrophages, 7 days post-infection. These cells suppressed 3H-thymidine-incorporation and lymphokine production in syngeneic lymphocyte cultures and hence appeared to have depressed accessory cell function, although interleukin-1 production and the capacity to take up colloidal gold were enhanced. The cytostatic activity was located in a low density fraction (1.05 g/ml), which was expanded by MCMV infection. The lowest density cells had higher frequencies of infection but the proportion of cells releasing virus (less than 0.2%) was below the proportion activated, as shown by the shift in the density profile or enhanced colloidal gold uptake. A comparable accumulation of cytostatic activated peritoneal macrophages occurred in mice treated with cyclosporine A, but nude mice showed macrophage activation without cytostasis, so the role of T cells is not resolved. The spleens of infected mice maintaining high levels of virus in this organ atrophied, and the remaining cells were unable to proliferate in culture. In contrast, mice clearing the virus developed splenomegaly and restricted responsiveness, which may be governed by cytostatic cells equivalent to those in the peritoneal cavity. The spread of virus to the lymph nodes was limited and MCMV-primed cells were readily demonstrable.