Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, USA.
Am J Reprod Immunol. 2012 Mar;67(3):184-97. doi: 10.1111/j.1600-0897.2011.01088.x. Epub 2011 Nov 13.
CD300a is an immunomodulatory molecule of the immunoglobulin receptor superfamily expressed in the leukocytes of myeloid and lymphoid lineages. However, its biological function on CD8+ T lymphocytes remains largely unknown. This study was conducted to assess the biological significance of CD300a expression in T lymphocytes and to determine whether its expression in peripheral T lymphocytes changes in pregnant women presenting with antifetal rejection.
Microarray analysis was performed using total RNA isolated from peripheral CD300a+ and CD300a- T lymphocytes. Flow cytometric analysis of the peripheral blood samples of pregnant women and pathologic examination of the placentas were conducted.
A large number of genes (N = 1245) were differentially expressed between CD300a- and CD300a+ subsets of CD8+ T lymphocytes, which included CCR7, CD244, CX3CR1, GLNY, GZMB, GZMK, IL15, ITGB1, KLRG1, PRF1, and SLAMF7. Gene ontology analysis of differentially expressed genes demonstrated enrichment of biological processes such as immune response, cell death, and signal transduction. CD300a expression in CD8+ T lymphocytes was coupled to a more cytotoxic molecular signature. Of note, the proportion of CD300a+CD8+ T lymphocytes increased in pregnant women with chronic chorioamnionitis (antifetal rejection of the chorioamniotic membranes; P < 0.05).
The findings of this study strongly suggest an increase in systemic T-lymphocyte-mediated cytotoxicity in pregnant women with chronic chorioamnionitis as a manifestation of maternal antifetal rejection.
CD300a 是免疫球蛋白受体超家族的一种免疫调节分子,在髓系和淋巴系白细胞中表达。然而,其在 CD8+T 淋巴细胞上的生物学功能在很大程度上尚不清楚。本研究旨在评估 CD300a 在 T 淋巴细胞中的表达的生物学意义,并确定其在外周 T 淋巴细胞中的表达是否在出现抗胎儿排斥的孕妇中发生变化。
使用从外周 CD300a+和 CD300a-T 淋巴细胞中分离的总 RNA 进行微阵列分析。对孕妇外周血样本进行流式细胞术分析,并对胎盘进行病理检查。
CD300a-和 CD300a+CD8+T 淋巴细胞亚群之间有大量基因(N=1245)表达差异,包括 CCR7、CD244、CX3CR1、GLNY、GZMB、GZMK、IL15、ITGB1、KLRG1、PRF1 和 SLAMF7。差异表达基因的基因本体分析表明,免疫反应、细胞死亡和信号转导等生物学过程得到富集。CD8+T 淋巴细胞中 CD300a 的表达与更具细胞毒性的分子特征相关。值得注意的是,患有慢性绒毛膜羊膜炎(绒毛膜羊膜炎对胎儿的排斥;P<0.05)的孕妇中 CD300a+CD8+T 淋巴细胞的比例增加。
本研究的结果强烈表明,慢性绒毛膜羊膜炎孕妇全身 T 淋巴细胞介导的细胞毒性增加,表现为母体抗胎儿排斥。