Background

Peripheral helper T (TPH) cells, a recently defined subset of Th cells, promote B cell differentiation and antibody production in inflamed tissues. This study investigated whether circulating TPH cells are associated with primary biliary cholangitis (PBC), a typical organ-specific autoimmune disease.

Methods

Twenty PBC patients and 20 age- and sex-matched healthy controls (HCs) were recruited. The circulating TPH cell subsets were analyzed by flow cytometry, and the associations of TPH cells with disease activity and plasma cells were determined. Functional analysis was performed using a TPH and B cell coculture experiment.

Results

The frequencies of circulating TPH cells, ICOS⁺ TPH cells, and CD28⁺ TPH cells were increased in patients with PBC. Furthermore, the ICOS⁺ TPH cell level was higher in PBC patients with or without cirrhosis than in HCs, and the level decreased after treatment. Moreover, ICOS⁺ TPH cell levels correlated positively with specific clinical parameters (including anti-mitochondrial antibodies against M2 antigen (AMA-M2), IgM) and plasma cell levels, suggesting that the TPH cell activation status is associated with the severity of PBC. Coculture results revealed an enhanced ability of TPH cells from PBC patients to induce B cell differentiation.

Conclusions

Elevated numbers of TPH cells may be involved in the pathogenesis of PBC, and the activation status of TPH cells is related to the severity of PBC. Additionally, TPH cells can be used as a useful biomarker for evaluating the progression of PBC and may serve as a therapeutic target for PBC patients in the future.

中文翻译：

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原发性胆源性胆管炎的循环外周血辅助T细胞扩增

背景

外围辅助T细胞（TPH）是Th细胞的最新定义，可促进B细胞分化和发炎组织中的抗体产生。这项研究调查了循环中的TPH细胞是否与典型的器官特异性自身免疫性疾病原发性胆管性胆管炎（PBC）相关。

方法

招募了20名PBC患者以及20名年龄和性别相匹配的健康对照（HCs）。通过流式细胞仪分析循环的TPH细胞亚群，并确定TPH细胞与疾病活动性和浆细胞的关联。使用TPH和B细胞共培养实验进行功能分析。

结果

PBC患者的循环TPH细胞，ICOS ⁺ TPH细胞和CD28 ⁺ TPH细胞的频率增加。此外，有或没有肝硬化的PBC患者的ICOS ⁺ TPH细胞水平均高于HCs，治疗后水平下降。此外，ICOS ⁺ TPH细胞水平与特定临床参数（包括针对M2抗原的抗线粒体抗体（AMA-M2），IgM）和浆细胞水平呈正相关，这表明TPH细胞激活状态与PBC的严重程度有关。共培养结果显示，来自PBC患者的TPH细胞诱导B细胞分化的能力增强。

结论

TPH细胞数量的增加可能参与了PBC的发病过程，而TPH细胞的激活状态与PBC的严重程度有关。此外，TPH细胞可用作评估PBC进展的有用生物标志物，并且将来可作为PBC患者的治疗靶标。