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Central Role of Interleukin-15 in Postovulatory Recruitment of Peripheral Blood CD16(–) Natural Killer Cells into Human Endometrium

Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan

Address all correspondence and requests for reprints to: Kotaro Kitaya, Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-Ku, Kyoto 602-8566, Japan. E-mail: kitaya{at}koto.kpu-m.ac.jp.

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 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 PB CD16(–) 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, 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.

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