The Costimulatory Signal Upregulation is Associated with Th1 Bias at the Maternal–Fetal Interface in Human Miscarriage

Authors

  • Li-Ping Jin,

    1. Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China
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    • These authors contributed equally to this work.

  • Deng-Xuan Fan,

    1. Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China
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    • These authors contributed equally to this work.

  • Tai Zhang,

    1. Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China
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  • Pei-Fen Guo,

    1. Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China
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  • Da-Jin Li

    1. Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China
    2. Department of Obstetrics & Gynecology, Hainan Medical College Affiliated Hospital, Haikou, China
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Da-Jin Li, Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics & Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, China.
E-mail: djli@shmu.edu.cn

Abstract

Citation Jin L-P, Fan D-X, Zhang T, Guo P-F, Li D-J. The costimulatory signal upregulation is associated with Th1 bias at the maternal–fetal interface in human miscarriage. Am J Reprod Immunol 2011; 66: 270–278

Problem  To evaluate whether the association of the costimulatory signal regulation with T helper 1/T helper 2 (Th1/Th2) bias at maternal–fetal interface in human pregnancy loss.

Method of study  The expression of CD80 and CD86 in decidual tissues and CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA-4) in the decidual T cells was compared between normal early pregnancy and miscarriage by qPCR and Western blot. The cytokine production in decidual T cells was performed by flow cytometry. The correlation of costimulatory molecule expression with Th1/Th2 cytokines was analyzed.

Results  The CD80 mRNA and protein expression showed no significant difference between normal pregnancy and miscarriage. An increase in the expression of CD28 and CD86 was accompanied by a decrease in the expression of CTLA-4 in miscarriage in comparison with the early pregnancy. The higher expression of interleukin (IL)-2 and interferon-γ (IFN-γ), and lower expression of IL-4 and IL-10 in the decidual T cells were present in miscarriage. A correlation analysis showed a significant positive correlation of CD86 and CD28 expression with the Th1 cytokine production (IL-2 and IFN-γ), a significant negative correlation of CTLA-4 expression with the Th1 cytokine production.

Conclusion  The upregualtion of costimulatory signals on T cells might form an abnormal immune microenvironment, a shift to Th1 responses, at maternal–fetal interface, which leads to human miscarriage.

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