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Effector Activity of Decidual CD8⁺ T Lymphocytes in Early Human Pregnancy¹

Schools of Surgical and Reproductive Sciences,³ Clinical and Laboratory Sciences,⁴ Medical Education Development,⁵ University of Newcastle-upon-Tyne, Newcastle-upon-Tyne, Tyne and Wear, NE1 4LP, United Kingdom

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 characterize 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 wks gestational age). Decidual CD8⁺ T lymphocytes were studied using standard and redirected chromium release assays to investigate natural killer cell-sensitive cytotoxicity and cytotoxicity that requires T-cell receptor signal transduction respectively, multiplex cytokine analysis to analyze 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 % Specific Chromium Release at effector:target ratio of 32:1 [SCR₃₂] of 32.7 ± 5.8) and against K562 target cells (mean SCR₃₂ of 20.3 ± 0.5). Phytohemagglutinin-P (PHA-P)-stimulated decidual CD8⁺ T lymphocytes produced high levels of both interferon gamma and interleukin (IL) 8, and low levels of granulocyte-macrophage colony-stimulating factor (CSF2), IL1B, IL2, IL6, IL10, IL12, and tumor necrosis factor; 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.

cytokines, decidua, immunology, trophoblast

¹ Supported by the Dr. William Edmund Harker Foundation, RVI, Newcastle-upon-Tyne, and the BBSRC (S19967).

² Correspondence: Roger F. Searle, Anatomy and Clinical Skills, School of Medical Education Development, University of Newcastle-upon-Tyne, Framlington Place, Newcastle-upon-Tyne NE2 4HH, United Kingdom. FAX: 44 191 222 5517; R.F.Searle{at}ncl.ac.uk

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