Cell-to-cell mediated inhibition of natural killer cell proliferation by monocytes and its regulation by histamine H2-receptors.

Human peripheral blood monocytes, recovered by counter-current centrifugal elutriation, suppressed interleukin-2 (IL-2)-induced proliferation of autologous lymphocytes, recovered from low density Percoll fractions. Cell sorting experiments, analysis of phenotype of proliferating cells, and removal of defined cellular subsets by complement cytotoxicity revealed that IL-2-induced proliferation was confined to CD3-/16+/56+ natural killer (NK) cells. Monocyte-induced suppression of NK-cell proliferation was completed within 1 h of incubation with monocytes and unrelated to the formation of prostaglandins or other intermediary factors. The biogenic amine histamine, acting via H2-type histamine receptors (H2R) on monocytes, completely counteracted the monocyte-mediated suppression of IL-2-induced NK-cell proliferation. Our data are suggestive of a H2R-regulated, cell-cell-mediated mechanism by which monocytes down-modulate NK-cell proliferation.