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BOR - Papers in Press, published online ahead of print June 11, 2008.
Biol Reprod 2008, 10.1095/biolreprod.107.066324
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Submitted October 25, 2007
Returned for revision December 19, 2007
Accepted May 16, 2008

Immunology


Expression and Function of PDCD1 at the Human Maternal-Fetal Interface

Elizabeth S. Taglauer , Ann S. Trikhacheva , Joyce G. Slusser , and Margaret G. Petroff *

* To whom correspondence should be addressed. E-mail: mpetroff{at}kumc.edu.

Abstract
The failure to reject the semiallogenic fetus by maternal T lymphocytes suggests that potent mechanisms regulate these cells. PDCD1 is a CD28 family receptor expressed by T cells, and its ligand CD274 is strongly expressed by trophoblast cells of the human placenta. In this study, we examined whether human maternal T cells express PDCD1. Immunofluorescence examination of uterine tissues revealed PDCD1 expression on CD3+ cells was low in non-pregnant endometrium but increased in first trimester decidua and remained elevated in term decidua (P < 0.05). In addition, higher relative proportions of term decidual CD8bright, CD4+, and regulatory T cells expressed PDCD1 in comparison to autologous peripheral blood (P < 0.05). Term decidual T cells also expressed full length and soluble PDCD1 mRNA isoforms more abundantly than their peripheral blood counterparts (P ≤ 0.05). We also examined the effects of PDCD1:CD274 interactions in decidual T cells. Jar choriocarcinoma cells were transfected with CD274 and co-cultured with activated decidual CD4+ or CD8bright T cells for 72 hours followed by analysis of cytokine concentration and decidual T cell apoptosis. As compared to empty vector transfected cells, CD274-transfected Jar cells caused a significant suppression of IFNG (IFN-gamma) and TNFA (TNF-alpha) production by CD4+ (P < 0.05) but not CD8bright T cells, while having no effect on secretion of IL10 or T cell apoptosis. These results suggest that the PDCD1:CD274 pathway functions in modification of maternal decidual lymphocyte cytokine secretion during pregnancy.

Key words: Decidua • Placenta • CD274 • PDCD1 • T cells





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