Regulation of Abortion by γλ T Cells

Authors

  • Petra C. Arck,

    1. McMaster University, Depts. of Medicine, Pathology, Obstetrics and Gynaecology, Hamilton, Ontario, Canada
    2. Amgen Institute, Princess Margaret Hospital, Toronto, Ontario, Canada
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  • David A. Ferrick,

    1. McMaster University, Depts. of Medicine, Pathology, Obstetrics and Gynaecology, Hamilton, Ontario, Canada
    2. Amgen Institute, Princess Margaret Hospital, Toronto, Ontario, Canada
    3. University of California at Davis, Dept. of Microbiology and Pathology, Davis, California.
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  • Darlene Steele-Norwood,

    1. McMaster University, Depts. of Medicine, Pathology, Obstetrics and Gynaecology, Hamilton, Ontario, Canada
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  • Ken Croitoru,

    1. McMaster University, Depts. of Medicine, Pathology, Obstetrics and Gynaecology, Hamilton, Ontario, Canada
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  • David A. Clark

    Corresponding author
    1. McMaster University, Depts. of Medicine, Pathology, Obstetrics and Gynaecology, Hamilton, Ontario, Canada
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McMaster University, Dept. of Medicine, Room 3V39, 1200 Main Street West, Hamilton, Ontario, Canada, L8N 3Z5.

Abstract

PROBLEM: T cells are present at the feto-maternal interface, but their function during pregnancy has not been fully elucidated. T cells bearing γλ T-cell receptor (TCR) may be particularly important, as some subsets can react to trophoblast cells by producing cytokines, such as interleukin-2 (IL-2).

METHOD: We depleted T cells bearing the γλ receptor by injecting monoclonal antibodies (mAB) into females of the abortion-prone animal model CBA x DBA/2. We investigated the percentage and number of γλ T-cell receptor positive (TCR)+ cells in decidua and spleen during pregnancy in control and γλ-depleted female mice. Pregnant females were also exposed to ultrasonic sound stress to boost the abortion rate.

RESULTS: Stress failed to increase the abortion rate in the γλ TCR-depleted mice. FACScan analysis show that the ratio of cells bearing the γλ TCR dramatically decreased after injection of mAB to the γλ TCR in spleen and decidua, these cells recovered six days after depletion, showing a change in cytokine pattern. Levels of TNF-α in decidual γλ T cells decreased; similar effects of decreasing Th1 cytokines could be observed in splenic γλ T cells. We further identified increased levels of intracellular TNF-α in the Vλ4 subset in the decidua, compared to spleen.

CONCLUSIONS: Trophoblast recognition by the Vλ4 T-cell subset in the decidua may cause the release of abortogenic cytokines such as TNF-α. Depletion of such γλ TCR T cells during early pregnancy may promote successful pregnancy outcome in normal pregnancy and prevent stress-induced abortions.

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