10.3389/fped.2019.00279.s007
Shuhao Zhang
Shuhao
Zhang
Shyamal Goswami
Shyamal
Goswami
Jiaqiang Ma
Jiaqiang
Ma
Lu Meng
Lu
Meng
Youping Wang
Youping
Wang
Fangming Zhu
Fangming
Zhu
Dandan Zhang
Dandan
Zhang
Shan Zheng
Shan
Zheng
Rui Dong
Rui
Dong
Xianmin Xiao
Xianmin
Xiao
Xiaoming Zhang
Xiaoming
Zhang
Gong Chen
Gong
Chen
Table_2_CD4+T Cell Subset Profiling in Biliary Atresia Reveals ICOS− Regulatory T Cells as a Favorable Prognostic Factor.DOCX
Frontiers
2019
biliary atresia
immune dysfunction
CD4+T cell subset
inducible co-stimulator
prognosis
2019-07-09 04:10:15
Dataset
https://frontiersin.figshare.com/articles/dataset/Table_2_CD4_T_Cell_Subset_Profiling_in_Biliary_Atresia_Reveals_ICOS_Regulatory_T_Cells_as_a_Favorable_Prognostic_Factor_DOCX/8830769
<p>Biliary atresia (BA) is a destructive pediatric liver disease and CD4<sup>+</sup>T cell activation is demonstrated to play an important role in BA. However, a comprehensive scenario regarding the involvement of CD4<sup>+</sup>T cell subsets to the development of BA remains unclear. Here, we aim to explore the infiltration of CD4<sup>+</sup>T cell subsets and their clinical significance in BA. In the present study, thirty BA liver samples were collected during surgery and were divided into good (BA1, n = 16) and poor prognosis (BA2, n = 14), with samples from choledochal cyst patients (n = 8) as control. By using multiplex immunohistochemistry, we evaluated the infiltration level of CD4<sup>+</sup>T cell subsets in the portal areas. RT-qPCR and flow cytometry were further applied to explore detailed features of Treg subsets. We revealed that hepatic infiltrating Th1, Th2, Th17, and ICOS<sup>+</sup>Treg cells were significantly increased in BA patients compared to controls and were negatively associated with prognosis, while high infiltrating ICOS<sup>−</sup>Tregs showed a favorable outcome. Phenotypic analysis indicated that, in contrast to ICOS<sup>+</sup>Tregs, ICOS<sup>−</sup>Tregs were mainly CD45RA<sup>hi</sup>CD45RO<sup>low</sup>, and preferentially expressed more CD73. Besides, RT-qPCR revealed elevated expression of CD25, CD73, TGF-β, and BCL-2 genes in ICOS<sup>−</sup>Tregs. Finally, functional assay confirmed that ICOS<sup>−</sup>Tregs had a higher suppressive capacity to cytokine secretion and were more resistant to apoptosis in vitro. Collectively, we demonstrate that a mixed immune response is involved in BA pathogenesis, and the globally enhanced effector CD4<sup>+</sup>T cell response is associated with unfavorable prognosis, highly suppressive ICOS<sup>−</sup>Tregs is a protective factor and may serve an important reference to predict prognosis.</p>