Differential effect of natural killer cells on modulating CFU-Meg and BFU-E proliferation in situ.

As a result of the striking discrepancy between the substantial amount of information on the role of natural killer (NK) cells derived from in vitro experimentation and the corresponding lack of data demonstrating their physiologic relevance, we have examined the importance of NK cells for the steady state production of hematopoietic stem and progenitor cells in situ. B6D2F1 mice received two 0.2-ml injections of ascites containing anti-NK 1.1 monoclonal antibody (anti-NK) directed to murine NK cells. Another group was treated similarly but received "control" ascites (CA) that was induced solely by injection of a mouse myeloma cell similar to the fusion partner of the NK 1.1 hybridoma. Two days after the last injection, we determined the number and cycling fraction (i.e., percentage of cells in S-phase determined by in vivo hydroxyurea suicide) of femoral stem cells (spleen colony-forming units; CFU-S) and committed granulocyte-macrophage (granulocyte-macrophage colony-forming units; CFU-GM), megakaryocytic (megakaryocyte colony-forming units; CFU-Meg), and erythroid (erythroid burst-forming units; BFU-E and erythroid colony-forming units; CFU-E) progenitor cells. The striking finding was the almost complete abolishment of the proliferation of CFU-Meg in the anti-NK group, resulting in a statistically significant (p less than 0.02) decrease in number to 37% of the CA control. In contrast, the cycling fraction of BFU-E was significantly (p less than 0.05) increased to 205% of the CA control with no increase in number. The number and cycling fraction of CFU-S, CFU-GM, and CFU-E in the anti-NK group were not significantly different from values in the control group. These findings add a novel aspect to the understanding of hematopoietic regulation by providing the first evidence for a differential effect of NK cells on the steady-state proliferation of CFU-Meg and BFU-E in situ.