Evidence for cytotoxic T-lymphocyte-target cell interaction in brains of mice infected intracerebrally with lymphocytic choriomeningitis virus.

Murine lymphocytic choriomeningitis is a T-cell-mediated pathologic immune phenomenon. The name of this experimental illness was derived from the principal histopathologic alterations of the central nervous system (CNS) of adult mice infected intracerebrally with lymphocytic choriomeningitis virus, i.e., lymphocytic infiltrations of plexus choroidei and meninges. The general assumption that the main event in the pathogenesis is damage to virus-infected target cells by cytotoxic T-lymphocytes is plausible but direct evidence is scarce. We have studied the ultrastructural alterations of both types of cells that are thought to participate in this immunopathologic interaction. Lymphocytes with signs of T-cell transformation were first evident on day 4 after infection. One day later, lymphoblasts, often extending uropods and containing cytoplasmic dense and compound multivesicular bodies, predominated. They were sometimes seen in intimate contact with connective tissue cells of the leptomeninx and epithelial cells of the choroid plexuses which were shown to be infected by immunofluorescence procedure. Lymphoblasts occasionally invaginated the cytoplasm of the putative target cells with cytoplasmic processes, and were even found inside the latter, exhibiting the phenomenon of emperipolesis. Lymphocytic transformation was at its maximum 6 days after infection. At this time, individual leptomeningeal cells and groups of plexus epithelial cells showed signs of cytolysis, and in a few instances these damaged cells were in close spatial association with lymphoblasts. Similar observations have been reported by others who studied the interaction between cytotoxic T-lymphocytes and their appropriate targeted cells in vitro. We interpret our findings as providing direct evidence for the assumption that one link in the chain of events leading to the cerebral form of lymphocytic choriomeningitis of the mouse is damage to virus-infected leptomeningeal and plexus cells by cytotoxic T-lymphocytes.