Strong natural killer (NK) cell activity in bone marrow of myeloma patients: accelerated maturation of bone marrow NK cells and their interaction with other bone marrow cells.

Abstract

Bone marrow natural killer (NK) cell activity was studied in patients with multiple myeloma. Bone marrow mononuclear cells from myeloma patients expressed considerable levels of cytotoxicity against K562 in a 4 h 51Cr-release assay, which was comparable to that of blood lymphocytes. In contrast, NK-cell activity was markedly low or absent in bone marrow of normal donors and control patients. Fractionation of bone marrow cells from myeloma patients on linear bovine serum albumin gradients enriched NK effector cells in the upper, lymphocyte-enriched fraction, with no reactivity in the middle fraction containing mainly myeloma cells. Treatment with either Leu-7 or OKMI monoclonal antibody plus complement reduced or abrogated bone marrow NK-cell activity of myeloma patients as well as blood NK-cell activity. However, OKMI plus complement failed to reduce control bone marrow NK-cell activity, although the activity was reduced by Leu-7 plus complement. Overnight exposure to interferon (IFN) of bone marrow cells resulted in an augmentation of NK-cell activity in myeloma patients, but not in controls. Furthermore, adherent bone marrow cells from controls suppressed IFN-induced enhancement of NK-cell activity of blood lymphocytes, whereas bone marrow of myeloma patients did not contain such suppressor cells. No cytotoxicity was induced in control bone marrow cells by cocultivation with bone marrow myeloma cells. Bone marrow NK cells from myeloma patients were able to lyse control bone marrow cells in a 18 h assay and their lytic activity was augmented by IFN treatment. However, neither bone marrow cells nor blood lymphocytes were cytotoxic to autologous and allogeneic fresh myeloma cells even after activation with IFN. These results suggest that NK precursor cells differentiate into HNK-I- and OKMI-positive mature NK cells in bone marrow of myeloma patients, but not in control bone marrow, and that these functional bone marrow NK cells may interact with other bone marrow elements.