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>