Identification of human lymphocyte-derived lymphotoxins with binding and cell-lytic activity on NK-sensitive cell lines in vitro

Abstract

Supernatants obtained from lectin-restimulated, preactivated, human peripheral blood lymphocytes rapidly released (5-24 hr) high levels of lymphotoxin (LT) activity in vitro. Peripheral blood lymphocytes were preactivated by coculturing with either fetal calf serum or with allogeneic continuous B-cell lines (LCCL) which were treated with mitomycin C. These supernatants contained a population of L-929 cell-lytic LT forms which also selectively bind to the NK-sensitive K-562 cell. However, lytic LT forms for L-929 cells from cPBL and LCCL cultures did not bind to the NK-sensitive MOLT-4 or NK-resistant Raji cells. Additional studies reveal these supernatants contain a second set of LT forms which have cell-binding and cell-lytic activity detectable on MOLT-4 and K-562 cells in a 12 to 18 hr 51Cr-release assay. Cell-lytic form(s) for the MOLT-4 and K-562 cells were not stable for more than a week at -20 degrees C. These findings indicate that materials with LT activity are heterogeneous with respect to their capacity to recognize common and discrete cell-surface components on different types of target cells in vitro.