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Peripheral CD300a+CD8+ T Lymphocytes with a Distinct Cytotoxic Molecular Signature Increase in Pregnant Women with Chronic Chorioamnionitis

Authors

  • Yi Xu,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, USA
    2. Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
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    • These authors contributed equally to this work.

  • Federica Tarquini,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, USA
    2. Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
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    • These authors contributed equally to this work.

  • Roberto Romero,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, USA
    2. Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
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  • Chong Jai Kim,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, USA
    2. Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
    3. Department of Pathology, Wayne State University School of Medicine, Detroit, MI, USA
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  • Adi L. Tarca,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, USA
    2. Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
    3. Department of Computer Science, Wayne State University, Detroit, MI, USA
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  • Gaurav Bhatti,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, USA
    2. Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
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  • JoonHo Lee,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, USA
    2. Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
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  • I. Birgitta Sundell,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, USA
    2. Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
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  • Pooja Mittal,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, USA
    2. Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
    3. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
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  • Juan Pedro Kusanovic,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, USA
    2. Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
    3. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
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  • Sonia S. Hassan,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, USA
    2. Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
    3. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
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  • Jung-Sun Kim

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, USA
    2. Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
    3. Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Jung-Sun Kim, Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul 135-710, Korea. E-mail: jsunkim@skku.edu and Roberto Romero, Perinatology Research Branch, NICHD, NIH, DHHS, Hutzel Women’s Hospital, 3990 John R St, Detroit, MI 48201, USA.
E-mail: prbchiefstaff@med.wayne.edu

Abstract

Citation Xu Y, Tarquini F, Romero R, Kim CJ, Tarca AL, Bhatti G, Lee J, Sundell IB, Mittal P, Kusanovic JP, Hassan SS, Kim J-S. Peripheral CD300a+CD8+ T lymphocytes with a distinct cytotoxic molecular signature increase in pregnant women with chronic chorioamnionitis. Am J Reprod Immunol 2012; 67: 184–197

Problem  CD300a is an immunomodulatory molecule of the immunoglobulin receptor superfamily expressed in the leukocytes of myeloid and lymphoid lineages. However, its biological function on CD8+ T lymphocytes remains largely unknown. This study was conducted to assess the biological significance of CD300a expression in T lymphocytes and to determine whether its expression in peripheral T lymphocytes changes in pregnant women presenting with antifetal rejection.

Methods of Study  Microarray analysis was performed using total RNA isolated from peripheral CD300a+ and CD300a− T lymphocytes. Flow cytometric analysis of the peripheral blood samples of pregnant women and pathologic examination of the placentas were conducted.

Results  A large number of genes (N = 1245) were differentially expressed between CD300a− and CD300a+ subsets of CD8+ T lymphocytes, which included CCR7, CD244, CX3CR1, GLNY, GZMB, GZMK, IL15, ITGB1, KLRG1, PRF1, and SLAMF7. Gene ontology analysis of differentially expressed genes demonstrated enrichment of biological processes such as immune response, cell death, and signal transduction. CD300a expression in CD8+ T lymphocytes was coupled to a more cytotoxic molecular signature. Of note, the proportion of CD300a+CD8+ T lymphocytes increased in pregnant women with chronic chorioamnionitis (antifetal rejection of the chorioamniotic membranes; P < 0.05).

Conclusion  The findings of this study strongly suggest an increase in systemic T-lymphocyte-mediated cytotoxicity in pregnant women with chronic chorioamnionitis as a manifestation of maternal antifetal rejection.

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