Inflammatory and immunological responses to murine cytomegalovirus in resistant CBA mice

Abstract

The resistance of CBA mice to MCMV is associated with the resistance of H-2k cells to infection in vitro, high NK and virus-specific DTH responses, and minimal accumulation of cytostatic peritoneal macrophages. This study investigates the functional capacity of lymphoid cells from infected CBA mice, using this strain as a model for successful control of CMV. Splenic viral replication was high 1-3 days p.i. and cell numbers were depressed, but T and B cells frequencies were maintained. The remaining spleen cells were hyporesponsive in culture and accessory cell function was marginally deficient. By 7 days p.i., virus titres declined, responsiveness increased and the residual defect was associated with cytostatic macrophages. The lymph nodes did not atrophy, exhibited low levels of viral replication and proliferative capacity was retained. The beige mutation did not affect the local response to intraperitoneal infection, but spleen cell numbers and responsiveness declined progressively. The results suggest the spleen may contribute to CMV disease by the replication of virus in susceptible cells until the NK response reduces virus titres and hence limits acute virus-induced immunosuppression. Macrophage-mediated suppression persisted in the spleen during recovery so clonal expansion of protective virus-primed T cells may occur predominantly in the lymph nodes.