NATURAL-KILLER (NK) CELLS ARE FUNCTIONALLY ABNORMAL AND NK CELL PROGENITORS ARE DIMINISHED IN GRANULOCYTE-COLONY-STIMULATING FACTOR-MOBILIZED PERIPHERAL-BLOOD PROGENITOR-CELL COLLECTIONS

Granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blo od progenitor cell (PBPC) collections are increasingly emerging as the graft of choice in many centers for autologous transplantation, and w ith increasing frequency for allogeneic transplantation. However, the role of myeloid cytokines in lymphoid function, lymphoid progenitors, and immune-mediated antitumor responses is not known. We studied PBPC collections from normal donors mobilized with G-CSF (10 mu g/kg). CD56 (+)/CD3(-) natural killer (NK) cells sorted from PBPC products exhibit ed a diminished ability to kill tumor targets, were less responsive in acquiring increased cytolysis with interleukin-2 (IL-2), and prolifer ated less than NK cells from normal unprimed peripheral blood. This ab normality was not explained by a change in phenotype of NK cells norma lly circulating in the blood after G-CSF administration. We could not demonstrate any direct suppressive effect on normal unprimed NK cell p roliferation or cytotoxicity by culture with pharmacologic concentrati ons of G-CSF. We next evaluated the effects of G-CSF on CD34(+) NK cel l progenitors. CD34(+)/CD2(+), CD34(+)/CD7(+), and CD34(+)/CD10(+) pro genitors were markedly diminished in G-CSF-mobilized PBPC products. CD 34(+) cells cultured in limiting dilution assays showed a sixfold decr ease in NK cell progenitors when derived from G-CSF-mobilized CD34(+) PBPCs compared with CD34(+) cells derived from unprimed marrow. The fi nding of decreased NK cell function, inhibited proliferation, and dimi nished cloning frequency after treatment with G-CSF could be mimicked in vitro by culture of primitive marrow progenitors (CD34(+), lineage- negative, HLA-DR-) on stromal layers in the presence of exogenous G-CS F. The findings presented here show that G-CSF administration to norma l donors decreases NK cell function and the relative frequency of NK c ell progenitors within the CD34(+) progenitor population. Overcoming t his diminished lymphoid capacity may be important to facilitate early post-transplant immunotherapy, Our in vitro model will be used in futu re studies to determine the mechanism of the G-CSF-induced suppression of NK cell progenitors, which may occur early in the differentiation process. (C) 1997 by The American Society of Hematology.