Demonstration of T-cell and K-cell cytotoxicity against measles-infected cells in normal subjects, multiple sclerosis and subacute sclerosing panencephalitis

Abstract

Mechanisms of cell-mediated cytotoxicity towards a human cell line persistently infected with measles virus were studied in fifteen normal (measles-immune) subjects, six patients with multiple sclerosis and three patients with subacute sclerosing panencephalitis. In normal subjects, cytotoxicity by peripheral blood mononuclear cells (PBM) in the absence of measles antibody was demonstrated, and shown by lymphocyte fractionation (removal of Fc receptor-bearing cells) to be T cell-mediated. The mean T cell-specific cytotoxic index after 12 hr incubation at the optimum target:effector cell ratio was 0·39±0·19 (1 s.d.). T-cell killing was inhibited by antibody in nine out of twelve subjects, and not significantly changed in three. Antibody enhancement of killing by PBM was found in seven out of fifteen normal subjects, but antibody did not enhance killing by a cell population depleted of Fc receptor-bearing cells. We therefore conclude that the antibody-dependent killing was mediated by Fc receptor-bearing cells (K cells). Mean cytotoxicity due to PBM in the presence of antibody at 12 hr was 0·59±0·25 (1 s.d.). Patients with multiple sclerosis showed significantly impaired T-cell cytotoxicity (mean ± 1 s.d. = 0·17±0·05), although there was overlap with the normal group, while PBM killing in the presence of antibody was normal (mean ± 1 s.d. = 0·60±0·07). Normal or low values for both types of cytotoxicity were found in three patients with subacute sclerosing panencephalitis. Contrary to evidence for several other viruses in mice, showing H-2 restriction of T-cell killing, we have demonstrated good T-cell cytotoxicity independent of shared HLA antigens between target and effector cell for measles virus infection.