Scanning and transmission electron microscopy study of antibody-dependent lymphocyte-mediated cytotoxicity on measles virus-infected cells

Abstract

The structural events related to antibody-dependent lymphocyte-mediated cytotoxicity (ADLC) have been studied on measles virus-infected cells using human peripheral blood lymphocytes (PBL) and anti-measles virus serum. The first event in ADLC was a recognition process occurring with 15 min after contact between the infected cells and lymphocytes. Plasma membrane and microvilli of adsorbed PBL were specifically attached to virus-induced ridges over nucleocapsids and to viral buds. After 30 min, a fraction of adsorbed PBL (K cells) changed shape and extended long filipodia toward the target cells which, in turn, showed long villi contacting the PBL. At 4 h, when cytotoxicity as measured by chromium release was maximum, K cells had flattened and numerous blebs and ruffles formed on their surface. The K-cell alterations varied in intensity with the type of measles-infected target cell, but frequently the K cells appeared irreversibly damaged. T- and non-T-cell fractions were separated, and in situ erythrocyte rosettes were used as markers for subpopulations which were easily recognized by scanning electron microscopy. Most of the cytotoxic K cells were identified as non-T cells carrying Fc receptors for immunoglobulin G. However, a small subpopulation of cells bearing both sheep erythrocyte and Fc receptors was also found to be involved in ADLC by chromium release assay as well as by electron microscopy. Some of these interacting T cells extended a long uropod on the target cell, but their intracellular structure remained unaltered through ADLC, in contrast with the other T cells and the non-t killer cells. This suggests that perhaps some T killer cells might remain functional after the cytotoxic interaction with a target cell.