Cell-mediated immunity to virus causing haemorrhagic fever with renal syndrome: generation of cytotoxic T lymphocytes.

Cytotoxic T lymphocytes (CTLs) were generated when spleen cells from mice infected with viruses causing haemorrhagic fever with renal syndrome were stimulated in vitro with syngeneic cells infected with viruses. These cytotoxic effector cells, with Lyt2+ L3T4- markers on their surface, demonstrated H-2 restriction. CTLs induced by Hantaan virus (76-118 strain) or Seoul virus (B-1 strain) showed cross-reactivity with infected target cells. Hantaan virus infection induced a higher CTLs response than Seoul virus infection, although the antibody responses to these two viruses and the replication of the two virus strains in athymic nude mice were not significantly different. Viral antigen detected with a monoclonal antibody reacting with nucleocapsid antigen was observed mainly in the cytoplasm of macrophages infected with Hantaan virus, but in the nucleus of cells infected with Seoul virus. The major viral antigens recognized by CTLs are discussed on the basis of these findings.