The expression of chemokine receptors in CD56(bright) CD16- natural killer cells and the mechanism of their recruitment in decidua

Abstract

To investigate the transcriptions of 18 chemokine receptors in human decidual natural killer (NK) cells and explore the possible mechanisms of preferential accumulation of CD56(bright)CD16(-)NK cells in decidua during first-trimester pregnancy. Villi and decidual tissue were collected from normal pregnant women with 5 approximately 10 gestational weeks by artificial abortion. The decidual CD56(bright)CD16(-)NK cells were isolated by immune magnetic beads. The transcription levels of 18 chemokine receptors in the decidual CD56(bright)CD16(-)NK cells were assessed by reverse transcription-polymerase chain reaction (RT-PCR). After the high expression of CXCR4 and CXCR3 mRNA in these cells was found, the expression of stromal cell-derived factor-1 (SDF-1), the specific ligand of CXCR4, in first-trimester human placenta was detected by in situ hybridization and immunohistochemistry. The concentration of SDF-1alpha in the supernatant of culture of isolated trophoblast cells derived from the first-trimester human placentas was measured by ELISA. The chemotaxis of SDF-1 to decidual CD56(bright)CD16(-)NK cells was tested in Transwell, and the chemotactic activity was quantitatively examined. Among the 18 chemokine receptors, CXCR4 and CXCR3 were found highly transcribed in decidual CD56(bright)CD16(-)NK cells. The concentration of SDF-1alpha in the supernatant was 385 ng/L +/- 91 ng/L after trophoblast cells had been cultured for 60 hours. Both rhSDF-1alpha and supernatants in the culture of trophoblast cells exhibited chemotactic activity on decidual CD56(bright)CD16(-)NK cells. When the concentration of rhSDF-1alpha was 10 micro g/L the number of cells that entered the lower chamber of Transwell accounted for 22.9% +/- 4.3% of the total calls. First-trimester human trophoblast cells produce SDF-1, which in turn endows the trophoblast cells with the capacity to attract decidual CD56(bright)CD16(-)NK cells highly expressing CXCR4. This activity contributes to the recruitment of decidual lymphocytes and may be used at a local level to manipulate the microimmune environment at the materno-fetal interface.