Decreased Expression of Cytotoxic Proteins in Decidual CD8+ T Cells in Preeclampsia

Abstract

In our study, we aimed to establish expression of cytotoxic CD8+ T cells in the decidua basalis and the maternal peripheral blood (mPBL) of severe and mild preeclampsia (PE) and compare to healthy pregnancies. Decidual tissue and mPBL of 10 women with mild PE, 10 women with severe PE, and 20 age-matched healthy pregnancy controls were analyzed by double immunofluorescence and qPCR, respectively. By double immunofluorescence staining, we found a decreased total number of cells/mm2 in decidua basalis of granulysin (GNLY)+ (p ˂ 0.0001), granzyme B (GzB)+(p ˂ 0.0001), GzB+CD8+(p ˂ 0.0001), perforin (PRF1)+ (p ˂ 0.0001), and PRF1+CD8+ (p ˂ 0.01) in the severe PE compared to control group. Additionally, we noticed the trend of lower mRNA expression for GNLY, granzyme A (GZMA), GzB, and PRF1 in CD8+ T cells of mPBL in mild and severe PE, with the latter marker statistically decreased in severe PE (p ˂ 0.001). Forkhead box P3 (FOXP3) mRNA in CD8+ T cells mPBL was increased in mild PE (p ˂ 0.001) compared to controls. In conclusion, severe PE is characterized by altered expression of cytotoxic CD8+ T cells in decidua and mPBL, suggesting their role in pathophysiology of PE and fetal-maternal immune tolerance.

Integration of circulating microRNAs and transcriptome signatures identifies early‐pregnancy biomarkers of preeclampsia

“…The enrichment of the PE gene signature for immunologic processes and cytokine production along with the observation of the association of a substantial number of these genes with PE in this and prior reports 2 highlight the presence of an immune‐mediated condition and importance of the maternal‐foetal interface in early to mid‐stages of pregnancy and PE development. The enhanced systemic inflammatory response in women with PE is also emphasised by the observation of genes such as CXCL8 ( IL‐8 ), CXCL10 and CD8A , as key regulators of the PE module, consistent with previous reports of dysregulation of these target genes in the disease 92–95 …”

“…The enhanced systemic inflammatory response in women with PE is also emphasised by the observation of genes such as CXCL8 (IL-8), CXCL10 and CD8A, as key regulators of the PE module, consistent with previous reports of dysregulation of these target genes in the disease. [92][93][94][95] These two CXCL genes, which directly interact with CD8A, were also part of the miRNA signature regulatory subnetwork in the LCC component of the PE module. The subnetwork enrichment in extracellular pathways (i.e., gene products that are secreted from a cell into interstitial fluid or blood) suggests placenta as a potential tissue source for further investigation.…”

Prognostic and predictive significance of VEGF, CD31, and Ang-1 in patients with metastatic clear cell renal cell carcinoma treated with first-line sunitinib

“…The process of double immunofluorescence staining was carried out according to the immunofluorescence protocols previously described [ 24 ].…”

CD226 knockout reduces the development of CD8+ T by impairing the TCR sensitivity of double‐positive thymocytes

“…Cluster 2 was identified by Granzyme A (Gzma), and Cluster 3 was identified by CD5 (Figure 4e). Granzyme A is an essential serine protease that is selectively expressed in CTLs and NK cells to induce the death of tumour and virus-infected cells [27,28], indicating that Gzma+ Cluster 2 may further develop into CD8+ T cells. These results demonstrated that CD226 knockout inhibited the development of DPT-Q and that the absence of the Gzma+ subcluster may be the underlying cause of CD8+ T developmental disorder.…”