CD4 + T Cell Subset Profiling in Biliary Atresia Reveals ICOS - Regulatory T Cells as a Favorable Prognostic Factor

• Published in: Frontiers in pediatrics 2019-07, Vol.7, p.279-279
• Main Authors: Zhang, Shuhao, Goswami, Shyamal, Ma, Jiaqiang, Meng, Lu, Wang, Youping, Zhu, Fangming, Zhang, Dandan, Zheng, Shan, Dong, Rui, Xiao, Xianmin, Zhang, Xiaoming, Chen, Gong
• Format: Article
• Language: English
• Subjects: biliary atresia; CD4+T cell subset; immune dysfunction; inducible co-stimulator; Pediatrics; prognosis
• ISSN: 2296-2360; 2296-2360
• DOI: 10.3389/fped.2019.00279

Biliary atresia (BA) is a destructive pediatric liver disease and CD4 T cell activation is demonstrated to play an important role in BA. However, a comprehensive scenario regarding the involvement of CD4 T cell subsets to the development of BA remains unclear. Here, we aim to explore the infiltration of CD4 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, = 16) and poor prognosis (BA2, = 14), with samples from choledochal cyst patients ( = 8) as control. By using multiplex immunohistochemistry, we evaluated the infiltration level of CD4 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 Treg cells were significantly increased in BA patients compared to controls and were negatively associated with prognosis, while high infiltrating ICOS Tregs showed a favorable outcome. Phenotypic analysis indicated that, in contrast to ICOS Tregs, ICOS Tregs were mainly CD45RA CD45RO , and preferentially expressed more CD73. Besides, RT-qPCR revealed elevated expression of β, and genes in ICOS Tregs. Finally, functional assay confirmed that ICOS Tregs had a higher suppressive capacity to cytokine secretion and were more resistant to apoptosis . Collectively, we demonstrate that a mixed immune response is involved in BA pathogenesis, and the globally enhanced effector CD4 T cell response is associated with unfavorable prognosis, highly suppressive ICOS Tregs is a protective factor and may serve an important reference to predict prognosis.