1154 Inhibition of Hemopoietic

A possible role for natural killer (NK) ~ cells in regulating hematopoiesis was originally suggested by Cudkowicz and Hochman (1) and Kiessling et al. (2), in the mouse system. These authors showed that parental hematopoietic or lymphoid grafts do not survive in lethally irradiated F1 hybrids, even though these animals are universal recipients of grafts of other types of parental tissues. Experiments (3, 4) evaluating the formation of colonies or the proliferation of bone marrow stem cells in the recipient spleen showed that cells with NK characteristics are responsible for the graft rejection. Direct destruction of bone marrow cells in vivo by NK cells has also been observed in experiments in which the clearance o f ~25I-uridine-labeled bone marrow cells after intravenous inoculation was measured (5). In humans, NK cells have been shown to react with cells from different lineages at early stages of differentiation, such as immature thyrnocytes (6, 7), bone marrow cells (6), and myeloid leukemic cells (8). Lymphocytes with NK cell characteristics are able to inhibit both myeloid and erythroid colony formation in vitro (9-15). There is also evidence for a possible pathogenetic in vivo role of such suppressor lymphocytes in patients with pure red cell aplasia associated with B cell chronic lymphatic leukemia (16, 17), aplastic anemia (18), and, more recently, in patients with NK lymphocytosis, in which the salient clinical feature is neutropenia (19, 20). Inhibition of hematopoiesis in vitro has been variously ascribed to direct interaction of NK cells with sensitive immature hemopoietic cell targets (6, 8, 1 !), to release of soluble factors from lymphocytes upon allogeneic or mitogenic stimulation (21, 22), or to both mechanisms operating together. Several soluble cell products, produced by different cell types, have also been shown to mediate suppression of hematopoietic colony formation. Among these are: (a) lactoferrin,