Effects of rIL-7 on Murine Bone Marrow NK Precursor Cells

We recently demonstrated that functional NK cells are produced from their precursors in murine long-term bone marrow cultures without the addition of exogenous growth factors. Because IL-7 is known to be produced by bone marrow stromal cells and is a proliferation factor for some immature cells of the B and T cell lineages, we tested whether rIL-7 could support the proliferation or maturation of NK precursor cells. By itself, rIL-7 did not induce NK lytic activity in cultures of unseparated bone marrow cells (BMC), but it did augment the response of unseparated BMC to 50 U rIL-2/ml, with a maximal enhancement at 10 ng IL-7/ml. Depletion experiments demonstrated that the IL-7-induced increase in cytotoxicity was not due to NK precursors, however, but to mature T and NK cells. IL-7 preferentially increased the number of CD8+ cells. Preculture of NK 1.1-depleted BMC with IL-7 did not increase the total number of NK 1.1+ cells or the lytic activity generated from NK precursor cells. However, IL-2-responsive NK lineage cells survived better in IL-7-supplemented medium than in medium alone. Thus, soluble rIL-7 did not expand the NK precursor cell population in vitro but it maintained the viability and subsequent responsiveness to IL-2 of NK precursors.