Central role of interleukin-15 in postovulatory recruitment of peripheral blood CD16(-) natural killer cells into human endometrium

A large number of CD16(-) natural killer (NK) cells appear in the human endometrium after ovulation. One possible explanation for this phenomenon is recruitment from peripheral blood (PB) CD16(-) NK cells. In this study, we examined whether IL-15 is involved in postovulatory recruitment from PB CD16(-) NK cells. The IL-15 receptor alpha chain was expressed on PB CD16(-) NK cells but not on CD16(+) NK cells. In an in vitro migration assay, recombinant human IL-15 enriched PBCD16( -) NK cells. Endometrial soluble protein fraction in the secretory phase, but not in the proliferative phase, also enriched these NK cells. Neutralization of IL-15 in the secretory phase endometrium with anti-IL-15 monoclonal antibody significantly lowered the enrichment of PB CD16(-) NK cells. In contrast, neutralization of other potential chemokines, including stromal cell-derived factor-1 or macrophage inflammatory protein-1 alpha, had no significant effect. The IL-15 concentration in the endometrial soluble protein fraction was higher in the secretory phase than in the proliferative phase, with a peak in the midsecretory phase. These results support the idea that endogenous IL-15 in secretory phase endometrium plays a central role in postovulatory recruitment of PB CD16(-) NK cells into the human endometrium.