In vitro morphological studies on antibody-dependent nonimmune lymphocyte-mediated cytotoxicity in chronic active liver disease

Using an in vitro system of antibody-dependent cellular cytotoxicity (ADCC), the killing effect of chronic liver disease sera on target Chang cells, mediated by effector nonimmune lymphocytes (NLy), was studied. NLy destroyed Chang cells in monolayers pretreated with sera of patients with chronic active liver disease (CALD). Sera from these patients with CALD, after receiving steroid therapy, demonstrated a significant decrease of the cytotoxic action of NLy. The target cells treated with sera of normal subjects or patients with chronic persistent hepatitis were only minimally affected. Morphological observations of the cytotoxic action in a CALD serum-treated group showed intimate contact between NLy and the target cells in the areas of the plaques, where large numbers of the target Chang cells were injured and were closely associated with effector NLy. The Chang cells developed cytoplasmic swelling. The surface became ruffled, and intracytoplasmic organelles displayed vesicular degeneration. Thereafter, cell rupture and fragmentation occurred. The sera in patients with CALD appear to possess a membrane reactive factor, presumably antibody, against the surface membrane of Chang cells. This immunological mode of reaction between the effectors and target cells (ADCC) may be important in the perpetuation and pathogenesis of hepatocyte death in CALD.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44386/1/10620_2005_Article_BF01073183.pd

An early history of T cell-mediated cytotoxicity.

After 60 years of intense fundamental research into T cell-mediated cytotoxicity, we have gained a detailed knowledge of the cells involved, specific recognition mechanisms and post-recognition perforin-granzyme-based and FAS-based molecular mechanisms. What could not be anticipated at the outset was how discovery of the mechanisms regulating the activation and function of cytotoxic T cells would lead to new developments in cancer immunotherapy. Given the profound recent interest in therapeutic manipulation of cytotoxic T cell responses, it is an opportune time to look back on the early history of the field. This Timeline describes how the early findings occurred and eventually led to current therapeutic applications