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BOR - Papers in Press, published online ahead of print July 5, 2006.
Biol Reprod 2006, 10.1095/biolreprod.106.052654
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Submitted March 22, 2006
Returned for revision April 28, 2006
Accepted June 16, 2006

Immunology


Effector Activity of Decidual CD8+ T Lymphocytes in Early Human Pregnancy

Paula J. Scaife , Judith N. Bulmer , Stephen C. Robson , Barbara A. Innes , and Roger F. Searle *

* To whom correspondence should be addressed. E-mail: r.f.searle{at}ncl.ac.uk.

Abstract
Although CD8+ T lymphocytes are present in human decidua throughout pregnancy, albeit as a minor population in early pregnancy, their role in normal pregnancy is largely unknown. The present study aimed to characterise their effector phenotype including cytolytic activity, cytokine profile and capacity to affect placental invasion. CD8+ lymphocytes were positively selected from normal early pregnancy decidua (7-14 weeks gestational age). Decidual CD8+ T lymphocytes were studied using standard and redirected chromium release assays to investigate NK cell sensitive cytotoxicity and cytotoxicity that requires T cell receptor signal transduction respectively, multiplex cytokine analysis to analyse cytokine production and a placental explant invasion model to assess the effect of soluble products of decidual CD8+ T lymphocytes on trophoblast invasion. Decidual CD8+ T lymphocytes exhibited cytolytic ability against P815 target cells (mean %SCR32 32.7 ± 5.8) and against K562 target cells (mean SCR32 20.3 ± 0.5). Phytohaemagglutinin-P (PHA-P) stimulated decidual CD8+ T lymphocytes produced high levels of both interferon gamma (IFNG) and interleukin (IL)8, and low levels of granulocyte-macrophage colony stimulating factor (CSF2), IL1B, IL2, IL6, IL10, IL12 and tumor necrosis factor (TNF); these did not vary with gestational age. IL4 was undetectable. Decidual CD8+ T lymphocyte supernatants increased the capacity of extravillous trophoblast cells to invade through Matrigel compared with the PHA-P control. These findings suggest that decidual CD8+ T cells can display cytolytic activity, do not evoke a predominant local intrauterine Th2 type cytokine environment and may act to regulate invasion of extravillous trophoblast cells into the uterus, a crucial process for normal uteroplacental development.

Key words: Immunology • Cytokines • Decidua • Trophoblast


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[Abstract] [Full Text] [PDF]




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