Generation of Natural Killer Cells From Both FcγRII/III+ and FCΓRII/III− Murine Fetal Liver Progenitors

Abstract

AbstractIn vitro culture of day-15.5 murine fetal liver (FL) cells in the presence of recombinant interleukin-2 (IL-2) results in the expansion of FcγRII/III + CD3-Ti−NK1.1+ cells displaying both natural killer (NK) and antibody-dependent cell cytotoxicity (ADCC) cytolytic activities. These FL-derived NK cells express FcγRIII (CD16) in association with an Fc∊Rl7 homodimer on their surface. In contrast, in vitro expansion of FL cells in the absence of IL-2 generates noncyto-toxic cells belonging to the myelomonocytic lineage (Mac1 +Gr1 +NK1.1−). Hence, IL-2 appears to be critical for the proliferation and differentiation of NK cells from FL progenitors. Experiments in which FL cells were fractionated by density gradient centrifugation before in vitro expansion showed that NK progenitors are contained within a cell population with a density of 1.04 < d < 1.08g/mL. Cells with d > 1.08 g/mL (representing ≥;40% of FL cells) have no such NK progenitor activity. In addition, after in-trathymic injection into Ly5 congenic host animals, day-15.5CD4−CD8− FL cells mature into CD4+CD8+ thymocytes within 12 days. Interestingly, this T-cell progenitor activity is restricted to subpopulations of FL cells that also contain NK progenitors, but is absent in high-density (d > 1.08 g/mL) FL cells. Finally, fractionation of FL cells according to surface expression of FcγRII/III complexes shows that NK (and T-lymphocyte) progenitors are found in both FcγRII/III+ and FCΓRII/III−FL subpopulations.