Humoral and cell-mediated immune mechanisms in the production of pathology in avirulent Semliki Forest virus encephalitis.

Seven days after peripheral inoculation with an avirulent strain of Semliki Forest virus, the brains of CBA and nude mice exhibited a mononuclear inflammation and spongiform degeneration. Mice that had received cyclophosphamide (150 mg/kg) 24 h after infection showed no pathology until day 11. However, immunofluorescence studies of the brains of immunosuppressed, infected mice demonstrated viral antigen within the soma and processes of neurons at earlier periods. The brain lesions could be reconstituted on day 7 in immunosuppressed, infected recipients with 6-day immune spleen cells. Immune spleen cells depleted of T lymphocytes, the non-immunoglobulin-bearing population deficient in B lymphocytes, or immune sera plus nonimmune bone marrow cells could also reconstitute the lesions. However, inflammation and spongiform changes were reduced when donor immune cells were depleted of either T or B lymphocytes. When both T and B lymphocytes were removed from the donor immune population, recipient brains did not show pathology. The results demonstrate that either antibody or immune T cells can trigger pathology, but there is also participation of nonimmune bone marrow-derived mononuclear cells, probably of the monocyte-macrophage lineage.