MONONUCLEAR CELL IN HUMAN-BLOOD WHICH MEDIATES ANTIBODY-DEPENDENT CELLULAR CYTOTOXICITY TO VIRUS-INFECTED TARGET-CELLS .1. IDENTIFICATION OF POPULATION OF EFFECTOR CELLS

Abstract

Mononuclear cells (MC) from human blood were fractionated by a variety of physical and immunologic techniques, and the cellular subpopulations generated were assessed for their capacity to lyse herpes simplex virus (HSV)-infected [human Change liver] target cells in the presence of Ig[immunoglobulin]G antibody to HSV. Latex phagocytosis and surface marker studies were performed in parallel to identify the major effector cells by their phagocytic properties and their possession of surface Ig and receptors for sheep erythrocytes, C3 [the 3rd complement component] or the Fc fragment of IgG. Cytotoxic effector cell activity was unaffected or slightly enhanced after the removal of plastic-adherent or carbonyl Fe-adherent MC, indicating that the major effector cell is not a classical monocyte. Similar results were obtained after removal of more than 90% of the T [thymus-derived] cells by depletion of rosette-forming cells. Effector cell activity was generally unchanged when more than 95% of the B [bone marrow-derived] cells were removed by filtering MC on nylon wool columns. Effector cell function was normal in 3 patients with B cell-deficient X-linked agammaglobulinemia. The effector cells are probably not T cells or B cells. A 4- to 5-fold enrichment in effector cells was consistently found in a subpopulation, consisting of 5% of the unfractionated MC, that was dramatically enriched for nonphagocytic cells with only Fc receptors (K [antibody-dependent killer] cells) and for nonphagocytic cells with no detectable surface markers (null cells). Since, as is demonstrated in the accompanying report, effector surface Fc receptors play a critical role in the mediation of antibody-dependent cellular cytoxicity directed at HSV-infected target cells, the major mononuclear effector cell in human blood is a K cell.