Maturation of murine natural killer precursor cells in the absence of exogenous cytokines requires contact with bone marrow stroma.

To test whether differentiation of natural killer (NK) precursor cells in unsupplemented long-term bone marrow culture requires contact with stromal cells, bone marrow cells (BMC) that were depleted of NK 1.1+ and Thy-1+ cells were cultured either directly on established, irradiated bone marrow stroma or in cell culture inserts separated from the stroma by a 0.45-micron microporous membrane. No exogenous cytokines were added. Depleted BMC produced NK 1.1+ nonlytic cells by day 7 and lytic NK 1.1+ cells by day 14 only when grown directly on the stroma. NK precursor cells survived in the inserts, however, and could respond to recombinant interleukin-2 in secondary culture. Thus, stromal cell-dependent proliferation and differentiation of lytic NK 1.1+ cells from their nonlytic NK 1.1- precursors requires direct interaction between stromal cells and NK precursors.