Rapid Generation of a Functional NK Cell Compartment (95.12)

Abstract

Abstract Anti-IL-2 antibodies have been used with the premise that they block IL-2 signaling in vitro and in vivo, but recent findings demonstrate that anti-IL-2 antibodies form a complex with IL-2 in vivo that actually enhances IL-2 activity. NK cells are one cell type affected by these IL-2 complexes. We asked at what stage IL-2 complexes act on NK cells and whether they could be utilized to generate functional NK cells with potential therapeutic value. We found that the administration of IL-2 complexes resulted in the rapid generation of NK cells in IL-15−/− animals. IL-15 is required for the development and survival of NK cells. Mature, transferred NK cells survived in IL-15−/− animals treated with IL-2 complexes, but proliferated only modestly. These data suggest that the IL-2 complex preferentially expands an immature subset of NK cells. To determine whether this expansion results in the generation of functional NK cells, we treated lethally irradiated, bone marrow reconstituted mice with IL-2 complexes and assessed the activity of NK cells by an in vivo killing assay. Bone marrow chimeras that were treated with IL-2 complexes displayed greatly enhanced NK lytic activity compared to control chimeras 4 days after initiation of treatment. We conclude that IL-2 complex has the potential to rapidly generate functional NK cells that may reduce the risk of viral infections and influence GVHD processes.