The antibody-dependent cell-mediated cytotoxic reaction. I. The morphological and functional heterogeneity of the rabbit cytotoxic cells.

The circulating WBC and cells of the various rabbit lymphoid organs (thymus, bone marrow, lymph nodes, appendix, sacculus rotundus and Peyer's patches) were systematically investigated for their capacity to mediate antibody-dependent cell-mediated cytotoxicity (ADCC). The target cells used were antibody-sensitized Cr-labelled chicken erythrocytes. Phagocytic cells and lymphocytes were capable of inducing lysis of these sensitized target cells and they might act rapidly or show a delay in the onset of activity depending upon the organ sources of these cells. Among the circulating cells, both mononuclear cells and heterophils showed ADCC activity. The cytotoxic cells in the different lymphoid organs could be distinguished from each other on the basis of the following criteria. (i) Rabbit WBC, spleen and bone marrow cells consistently exhibited cytotoxic activity early in culture with the target cells (6–8 h), with activity levelling off by 24–48 h. In contradistinction, the cells of the gut-associated lymphoid tissues (appendix, sacculus rotundus and Peyer's patches), thymus and lymph nodes did not display significant cytotoxic activity until 48–72 h of culture. (ii) Removal of phagocytic cells from the WBC, spleen and lymph node cells resulted in almost total loss of ADCC activity. On the other hand, the ADCC cytotoxic activity of the thymus and bone marrow cells was not significantly affected following removal of phagocytic cells. (iii) The cytotoxic activity of the WBC, spleen and lymph node cells was inhibited by soluble aggregates of rabbit gammaglobulin whereas that of the bone marrow and thymus cells was not. Rabbit ADCC cytotoxic cells could therefore be classified into a number of categories on the basis of their capacity to demonstrate immediate or delayed cytotoxic activity, their phagocytic or non-phagocytic properties and the susceptibility or lack of susceptibility of their ADCC cytotoxic activity to be inhibited by aggregates of gammaglobulin. It was therefore concluded that the ADCC effector cells in the rabbit parenchymal organs were heterogeneous. The circulating effector cells (the heterophils and monocytes), however, appeared to constitute functionally homogeneous populations of cells.