Dataset Information

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

ABSTRACT: 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, 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⁺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^hiCD45RO^low, and preferentially expressed more CD73. Besides, RT-qPCR revealed elevated expression of CD25, CD73, TGF-?, and BCL-2 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 in vitro. 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.

SUBMITTER: Zhang S

PROVIDER: S-EPMC6637302 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Zhang Shuhao S Goswami Shyamal S Ma Jiaqiang J Meng Lu L Wang Youping Y Zhu Fangming F Zhang Dandan D Zheng Shan S Dong Rui R Xiao Xianmin X Zhang Xiaoming X Chen Gong G

Frontiers in pediatrics 20190709

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 ( ...[more]

PMID: 31355166

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Project description:BackgroundRegulatory T cells are known to play a key role to counter balance the protective immune response and immune mediated pathology. However, the role of naturally occurring regulatory cells CD4+CD25+Foxp3+ in malaria infection during the disease pathogenesis is controversial. Beside this, ICOS molecule has been shown to be involved in the development and function of regulatory T cell enhance IL-10 production. Therefore, possible involvement of the ICOS dependent regulatory CD4+ICOS+Foxp3+ T cells in resistance/susceptibility during malaria parasite is explored in this study.Methods5 × 105 red blood cells infected with non-lethal and lethal parasites were inoculated in female Balb/c mice by intra-peritoneal injection. Infected or uninfected mice were sacrificed at early (3rd day post infection) and later stage (10th day post infection) of infection. Harvested cells were analysed by using flow cytometer and serum cytokine by Bioplex assay.ResultsThin blood films show that percentages of parasitaemia increases with disease progression in infections with the lethal malaria parasite and mice eventually die by day 14th post-infection. Whereas in case of non-lethal malaria parasite, parasitaemia goes down by 7th day post infection and gets cleared within 13th day. The number of CD4+ ICOS+ T cells increases in lethal infection with disease progression. Surprisingly, in non-lethal parasite, ICOS expression decreases after day 7th post infection as parasitaemia goes down. The frequency of CD4+ICOS+FoxP3+ Tregs was significantly higher in lethal parasitic infection as compared to the non-lethal parasite. The level of IL-12 cytokine was remarkably higher in non-lethal infection compared to the lethal infection. In contrast, the level of IL-10 cytokines was higher in lethal parasite infection compared to the non-lethal parasite.ConclusionTaken together, these data suggest that lethal parasite induce immunosuppressive environment, protecting from host immune responses and help the parasite to survive whereas non-lethal parasite leads to low frequencies of Treg cells seldom impede immune response that allow the parasite to get self-resolved.

Project description:BackgroundThyroid tissue has a special immune microenvironment that is not well characterized. Whether immune cells have a prognostic value in the recurrence of papillary thyroid cancer (PTC) needs further investigation.MethodsMultinodular non-toxic goiter (MNG) was taken as normal tissue for the difficulty in obtaining completely normal thyroid tissue (normal thyroid function, no thyroiditis, and no nodules). We compared the composition of mononuclear cells (MNCs) in peripheral blood and thyroid tissues from MNG and PTC patients by high-dimensional flow cytometry profiling and verified the results by multiplex immunohistochemistry. The recurrence rates of PTC patients with different CD8+T cell subset signatures were compared using TCGA database.ResultsWe observed that the immune cell composition of MNG was different from that in peripheral blood. Thyroid tissue contains higher percentages of T cells and NK cells. Moreover, the percentages of memory T cells and Treg cells were higher in thyroid than in peripheral blood and increased in PTC tumors. We further focused on the antitumoral CD8+T cells and found that the expression patterns of PD-1, CD39, and CD103 on CD8+T cells were different between MNG and PTC. Importantly, we found higher percentages of PD-1+CD39+CD103+CD8+T and PD-1+CD39+CD103-CD8+T cells in PTC tumor tissues from recurrent patients than non-recurrent patients. By analyzing PTC data from TCGA database, we found that the expression patterns of these molecules were associated with different pathologic types and genders among PTC patients. Moreover, patients with PD-1hiCD39loCD103hiCD8hi, PD-1hiCD39hiCD103loCD8hi, and PD-1loCD39hiCD103hiCD8hi expression patterns have a higher 10-year recurrence-free survival.ConclusionThe immune microenvironment in MNG tissue is distinct from that in peripheral blood and paratumor tissue. More memory CD8+T cells were detected in PTC, and expression patterns of PD-1, CD39, and CD103 on CD8+T cells were significantly different in physiology and gender and associated with the recurrence rate of PTC. These observations indicate that CD8+T cell signatures may be useful prognostic markers for PTC recurrence.

Dataset Information

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

Publications

CD4<sup>+</sup>T Cell Subset Profiling in Biliary Atresia Reveals ICOS<sup>-</sup> Regulatory T Cells as a Favorable Prognostic Factor.

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