Tilburgs Tamara, Schonkeren Dorrith, Eikmans Michael, Nagtzaam Nicole M, Datema Gert, Swings Godelieve M, Prins Frans, van Lith Jan M, van der Mast Barbara J, Roelen Dave L, Scherjon Sicco A, Claas Frans H
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
J Immunol. 2010 Oct 1;185(7):4470-7. doi: 10.4049/jimmunol.0903597. Epub 2010 Sep 3.
During pregnancy, maternal lymphocytes at the fetal-maternal interface play a key role in the immune acceptance of the allogeneic fetus. Recently, CD4(+)CD25(bright) 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.
在孕期，胎儿 - 母体界面处的母体淋巴细胞在对同种异体胎儿的免疫接纳中起关键作用。最近研究表明，CD4(+)CD25(bright)调节性T细胞集中于蜕膜组织，在那里它们能够抑制针对胎儿的特异性和非特异性免疫反应。蜕膜CD8(+)T细胞是在胎儿 - 母体界面识别并应答胎儿HLA - C的主要细胞类型，但关于这些细胞特征的数据有限。在本研究中，我们使用九色流式细胞术检测了蜕膜和外周血中CD8(+)T细胞群体的CD45RA、CCR7、CD28和CD27表达情况。我们的数据表明，蜕膜CD8(+)T细胞主要由分化的CD45RA(-)CCR7(-)效应记忆（EM）细胞组成，而未致敏的CD45RA(+)CCR7(+)初始细胞几乎不存在。与外周血EM CD8(+)T细胞相比，蜕膜EM CD8(+)T细胞中穿孔素和颗粒酶B的表达显著降低，这在蜕膜组织切片的免疫组化中得到了证实。有趣地是，定量PCR分析表明，与外周血EM CD8(+)T细胞相比，蜕膜EM CD8(+)T细胞中穿孔素和颗粒酶B的mRNA含量增加。蜕膜EM T细胞中高水平的穿孔素和颗粒酶B mRNA表明，蜕膜CD8(+)T细胞采用了EM细胞分化的替代方式，这可能包括对穿孔素和颗粒酶B mRNA翻译为功能性穿孔素和颗粒酶B蛋白的阻断。蜕膜CD8(+)T细胞分化的调节可能在母体对同种异体胎儿的免疫耐受中起关键作用。
