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Cytokine Profile of Natural Killer Cells in Early Human Pregnancy

Authors


Address reprint requests to Shigeru Saito, Department of Obstetrics and Gynecology, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama-shi, Toyama, 930-0194, Japan.
E-mail: s30saito@ms.toyama-mpu.ac.jp

Abstract

Problem:  To examine whether the NK1/NK2/NK3/NKr1 paradigm can be adapted in natural killer (NK) cells.

Method of study:  Mononuclear cells were isolated from peripheral blood and/or decidua in healthy non-pregnant women (n = 17), early pregnant women (6–12 weeks of gestation, n = 17) and miscarriage cases (6–11 weeks of gestation, n = 10). We investigated the production of transforming growth factor (TGF)-β, interleukin (IL)-4, IL-5, IL-10, IL-13, interferon (IFN)-γ and tumor necrosis factor-α from peripheral blood- and decidual-CD56bright NK cells and -CD56dim NK cells by flow cytometry.

Results:  In the peripheral blood of the non-pregnant subjects, the main populations of CD56bright NK cells and CD56dim NK cells were IFN-γ-producing NK1 type cells. Populations of IL-10-producing NKr1 type cells in peripheral blood CD56bright NK cells and CD56dim NK cells in early pregnant women were significantly greater compared with those in non-pregnant women, and these cells population decreased in miscarriage cases. In the early pregnancy decidua, the main populations of CD56bright NK cells and CD56dim NK cells were TGF-β-producing NK3 type cells, and NK1 type cells were rare. NK3 type cells in decidua were significantly decreased in miscarriage cases compared with those in normal pregnant subjects. IL-4-, IL-5- or IL-13-producing NK2 type cells were rare in peripheral blood and decidua.

Conclusion:  These data support the NK1/NK2/NK3/NKr1 hypothesis. NKr1 type cells in peripheral blood and NK3 type cells in decidua might play some important roles in the maintenance of pregnancy by regulation of maternal immune function.

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