ROLE OF SPLEEN MACROPHAGES IN INNATE AND ACQUIRED IMMUNE-RESPONSES AGAINST MOUSE HEPATITIS-VIRUS STRAIN A59

Owing to their scavenging and phagocytic functions, spleen macrophages are regarded to be important in the induction and maintenance of both innate and acquired immune defence mechanisms. In this study, we inve stigated the role of spleen macrophages in immunity against mouse hepa titis virus strain A59 (MHV-A59). Previous studies showed that spleen and liver macrophages are the first target cells for infection by MHV- A59 in vivo, suggesting that they could be involved in the induction o f immune responses against MHV-A59. We used a macrophage depletion tec hnique to deplete macrophages in vivo and studied the induction of vir us-specific antibody and cytotoxic T-cell (CTL) responses and non-immu ne resistance against MHV-A59 in normal and macrophage-depleted mice. Virus titres in spleen and liver increased rapidly in macrophage-deple ted mice, resulting in death of mice within 4 days after infection. El imination of macrophages before immunization with MHV-A59 resulted in increased virus-specific humoral and T-cell proliferative responses. H owever, virus-specific CTL responses were not altered in macrophage-de pleted mice. Our results show that spleen macrophages are of major imp ortance as scavenger cells during MHV-A59 infection and are involved i n clearance of virus from the host. In addition, macrophages may be in volved in the regulation of acquired immune responses. In the absence of macrophages, increased virus-specific T-cell and antibody responses are detectable, suggesting that macrophages suppress MHV-A59-specific T-and B-cell responses and that other cells serve as antigen-presenti ng cells.