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Altered carcinoembryonic antigen-related cell adhesion molecule 1/T-Cell immunoglobulin mucin-3 signaling causes the dysregulation of decidual CD8+T cells in the third trimester during preeclamptic pregnancies

1 Laboratory for Reproductive Immunology, NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, China
2 Department of Obstetrics, Obstetrics and Gynecology, Hospital of Fudan University, Shanghai 200090, China

Correspondence Address:
Ying Zhang,
Department of Obstetrics, Obstetrics and Gynecology, Hospital of Fudan University, No. 128 Shenyang Road, Shanghai 200090
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2096-2924.325828

Objective: To investigate the frequency and function of Tim-3+CD8+T cells in the third trimester of normal pregnancies (NPs) and preeclamptic (PE) pregnancies. Methods: T-cell immunoglobulin mucin-3 (Tim-3) expression levels of CD8+T cells in the decidua, peripheral blood, and umbilical cord blood obtained from women showing NPs and PE pregnancies were analyzed using flow cytometry. Decidual CD8+T cells were cultured in the presence of recombinant human carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) protein and/or Tim-3-specific neutralizing antibodies for analyzing CD107a and intracellular cytokine expression. The placental CEACAM1 protein expression was analyzed using immunohistochemistry. Results: Tim-3+CD8+T cells were more abundant in the decidua than in the peripheral blood. Tim-3 expression in the decidual CD8+T cells was significantly lower in PE patients. Decidual Tim-3+CD8+T cells from PE patients expressed higher levels of CD107a and the Th1-type cytokine IFN-γ, but lower levels of the Th2-type cytokine IL-4. CEACAM1 altered the CD107a, IFN-γ, and IL-4 levels; this was reversed by anti-Tim-3 antibodies. The CEACAM1 protein levels were lower in the placental tissues of women with PE pregnancies than in those of women with NPs. Conclusions: Abnormal CEACAM1/Tim-3 regulation may participate in the development of PE, accompanied by disturbed Th2 cell predominance and higher cytotoxicity of decidual CD8+T cells.

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