Human peripheral null lymphocytes. II. Producers of type-1 interferon upon stimulation with tumor cells, Herpes...

Human blood lymphocytes, exposed for 6 to 24 h in vitro to tumor cells (K 562, IGR3, L1210), Herpes simplex virus type 1 (HSV) or Corynebacterium parvum (CP), produced high levels of anti-viral activity which was identified as type-1 interferon (IF). In mixed lymphocyte tumor cell cultures (MLTC), the generated type-1 IF was definitely shown to originate from the lymphocytes and not from the tumor cells. Supplementation of leukocyte cultures with 10% fetal calf serum instead 10% human AB serum had little influence on tumor cell-induced IF production, but strongly reduced CP-induced IF production. Lymphocyte fractionation procedures involving iron/plastic treatment, nylon wool columns, Ig-anti-Ig columns and rosette (E, EA) separation led to the identification of null cells as highly efficient producers of type-1 IF. T cells obtained by different ways (E-rosette sedimentation, passage through 1 nylon and 2 Ig-anti-Ig columns, or thoracic duct lymphocytes) were poor IF producers in response to tumor cells, HSV and CP, but secreted anti-viral activity when stimulated with phytohemagglutinin. In MLTC, the level of generated type-1 IF roughly stimulated with phytohemagglutinin. In MLTC, the level of generated type-1 IF roughly paralleled nautral killer (NK) cell activity. Evidence is presented that type-1 IF can be produced by an Fc receptor-negative null cell subset, whereas NK activity requires Fc receptor-positive cells. It is suggested that production of type-1 IF represents one of the earliest functions in the differentiation process of mononuclear phagocytes and is likely to develop before the appearance of Fc receptors, diffuse esterase staining and latex phagocytosis.