NK cell subsets in the regulation of murine hematopoiesis: I. 5E6⁺ NK cells promote hematopoietic growth in H-2^d strain mice

NK cells are able to reject bone marrow allografts in lethally irradiated mice. 5E6 is a marker expressed on a subset of NK cells that is responsible for the rejection of H-2^d homozygous bone marrow cell (BMC) allografts. This suggests that the 5E6⁺ NK cell subset somehow recognizes and is deleterious for H-2^d BMC. However, unlike Ly-49⁺ NK cells, 5E6⁺ cells are not deleted or even down-regulated in H-2^d-homozygous mice. We wanted to determine, therefore, the role of the 5E6⁺ and 5E6^- NK cell subsets in the normal physiologic regulation of hematopoiesis in H-2^d strains of mice. Surprisingly, both in vivo depletion studies of normal mice and studies in which the subsets were purified and cultured with syngeneic BMC in vitro demonstrated that in H-2^d mice, the 5E6⁺ subset of NK cells did not inhibit, but instead promoted, growth of H-2^d BMC. Depletion of the 5E6⁺ subset also resulted in decreased marrow engraftment after syngeneic bone marrow transplantation in H-2^d mice. Analysis of the cell culture supernatants of the purified subsets indicated that the functional effects of the subsets on hematopoiesis correlated with the relative amounts of hematopoietic growth-promoting cytokines produced by the NK cells. These results demonstrate that physiologically relevant subsets of NK cells exist that are involved in the homeostatic regulation of hematopoiesis and that they can be distinguished on the basis of 5E6 expression.