Human Decidual Tissue Contains Differentiated CD8+ Effector-Memory T Cells with Unique Properties

Abstract

During pregnancy, maternal lymphocytes at the fetal–maternal interface play a key role in the immune acceptance of the allogeneic fetus. Recently, CD4+CD25bright regulatory T cells have been shown to be concentrated in decidual tissue, where they are able to suppress fetus-specific and nonspecific immune responses. Decidual CD8+ T cells are the main candidates to recognize and respond to fetal HLA-C at the fetal–maternal interface, but data on the characteristics of these cells are limited. In this study we examined the decidual and peripheral CD8+ T cell pool for CD45RA, CCR7, CD28, and CD27 expression, using nine-color flow cytometry. Our data demonstrate that decidual CD8+ T cells mainly consist of differentiated CD45RA−CCR7− effector-memory (EM) cells, whereas unprimed CD45RA+CCR7+ naive cells are almost absent. Compared with peripheral blood EM CD8+ T cells, the decidual EM CD8+ T cells display a significantly reduced expression of perforin and granzyme B, which was confirmed by immunohistochemistry of decidual tissue sections. Interestingly, quantitative PCR analysis demonstrates an increased perforin and granzyme B mRNA content in decidual EM CD8+ T cells in comparison with peripheral blood EM CD8+ T cells. The presence of high levels of perforin and granzyme B mRNA in decidual EM T cells suggests that decidual CD8+ T cells pursue alternative means of EM cell differentiation that may include a blockade of perforin and granzyme B mRNA translation into functional perforin and granzyme B proteins. Regulation of decidual CD8+ T cell differentiation may play a crucial role in maternal immune tolerance to the allogeneic fetus.