Immunoregulation by lymphokines: immune interferon and lymphotoxin induction of lymphokine activity in human peripheral blood leukocyte cultures.

Abstract

Supernatants of mitogen-induced human PBL cultures contain several lymphokine activities. Analysis of kinetic studies has suggested a correlation in the appearance in culture supernatants of lymphotoxin (LT) and immune interferon (Im-IF). We investigated this interaction between LT and Im-IF in the serum-free human PBL culture system. Partially purified LT was derived from a normal cell line, RPMI 1788. This LT, which had no contaminating IF activity, induced production of significant levels of IF activity as early as 15 hours after initiation of culture. This induced IF activity was identified as Im-IF by criteria of pH 2, SDS and heat sensitivity, as well as neutralization by AB to Im-IF. LT activity, in excess of the units added to the culture, was also measured in the LT-induced cultures. In another group of experiments, partially purified human Im-IF, produced by expression of a cloned gene in monkey COS-7 cells, was added to human PBL cultures. This Im-IF, at concentrations of 160 and 320 units/ml, caused induction of LT activity. The induced LT activity was neutralized by AB raised to 1788-derived LT. Im-IF treated cultures also contained IF activity in excess of the titers added to the cultures. These results would suggest an interaction between LT and Im-IF at the level of production by lymphoid cells.