Characterization of neutralizing anti-mouse IL-15 antibodies (96.15)

Abstract

Abstract IL-15 is believed to play a central role in the pathogenesis of a wide variety of disease states. We have developed neutralizing anti-mouse IL-15 antibodies from IL-15-null mice immunized with E.coli-derived recombinant mIL-15. Monoclonal antibodies M96 and M95 blocked the mIL-15-induced proliferation of CTLL-2 cells in vitro. In a mouse acute GVHD model, M96 inhibited donor CTL expansion and limited donor anti-host cytotoxic activity. In normal mice M96 induced a profound loss of NK cells and, though the total number of CD8 T cells, CD4 T cells, and B cells was not affected by M96, there was a slight reduction in the number of memory CD8 T cells in M96-treated mice. During time course studies, mice treated with 10μg of M96 lost about 50% of NK cells from the spleens within the first day and 95% of NK cells were eliminated by day 4. By day 14 the mice had recovered about 75-80% of their splenic NK cells, and by day 28 splenic NK cell levels were indistinguishable from untreated controls. We believe that M96 will be a useful tool for dissecting the roles of IL15 in normal homeostasis and inflammatory diseases.