Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, 3508 Utrecht, The Netherlands.
Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, 3508 Utrecht, The Netherlands.
Int J Mol Sci. 2023 Jul 26;24(15):11952. doi: 10.3390/ijms241511952.
Primary Sjögren's syndrome (pSS) is an autoimmune disease characterised by B cell hyperactivity. CXCR5+ follicular helper T cells (Tfh), CXCR5-PD-1hi peripheral helper T cells (Tph) and CCR9+ Tfh-like cells have been implicated in driving B cell hyperactivity in pSS; however, their potential overlap has not been evaluated. Our aim was to study the overlap between the two CXCR5- cell subsets and to study their PD-1/ICOS expression compared to "true" CXCR5/PD-1/ICOS-expressing Tfh cells. CXCR5- Tph and CCR9+ Tfh-like cell populations from peripheral blood mononuclear cells of pSS patients and healthy controls (HC) were compared using flow cytometry. PD-1/ICOS expression from these cell subsets was compared to each other and to CXCR5+ Tfh cells, taking into account their differentiation status. CXCR5- Tph cells and CCR9+ Tfh-like cells, both in pSS patients and HC, showed limited overlap. PD-1/ICOS expression was higher in memory cells expressing CXCR5 or CCR9. However, the highest expression was found in CXCR5/CCR9 co-expressing T cells, which are enriched in the circulation of pSS patients. CXCR5- Tph and CCR9+ Tfh-like cells are two distinct cell populations that both are enriched in pSS patients and can drive B cell hyperactivity in pSS. The known upregulated expression of CCL25 and CXCL13, ligands of CCR9 and CXCR5, at pSS inflammatory sites suggests concerted action to facilitate the migration of CXCR5+CCR9+ T cells, which are characterised by the highest frequencies of PD-1/ICOS-positive cells. Hence, these co-expressing effector T cells may significantly contribute to the ongoing immune responses in pSS.
原发性干燥综合征（pSS）是一种以 B 细胞过度活跃为特征的自身免疫性疾病。CXCR5+滤泡辅助 T 细胞（Tfh）、CXCR5-PD-1hi 外周辅助 T 细胞（Tph）和 CCR9+Tfh 样细胞已被认为参与驱动 pSS 中的 B 细胞过度活跃；然而，它们的潜在重叠尚未得到评估。我们的目的是研究这两种 CXCR5-细胞亚群之间的重叠，并研究它们的 PD-1/ICOS 表达与“真正的”CXCR5/PD-1/ICOS 表达的 Tfh 细胞相比。使用流式细胞术比较 pSS 患者和健康对照者（HC）外周血单个核细胞中的 CXCR5-Tph 和 CCR9+Tfh 样细胞群。考虑到这些细胞亚群的分化状态，将其 PD-1/ICOS 表达与彼此以及 CXCR5+Tfh 细胞进行比较。CXCR5-Tph 细胞和 CCR9+Tfh 样细胞，无论是在 pSS 患者还是 HC 中，都显示出有限的重叠。表达 CXCR5 或 CCR9 的记忆细胞中 PD-1/ICOS 表达较高。然而，在 CXCR5/CCR9 共表达的 T 细胞中发现了最高的表达，这些细胞在 pSS 患者的循环中丰富。CXCR5-Tph 和 CCR9+Tfh 样细胞是两种不同的细胞群，在 pSS 患者中均丰富，并可驱动 pSS 中的 B 细胞过度活跃。在 pSS 炎症部位已知上调表达的 CCL25 和 CXCL13 是 CCR9 和 CXCR5 的配体，提示协同作用以促进 CXCR5+CCR9+T 细胞的迁移，这些细胞的 PD-1/ICOS 阳性细胞频率最高。因此，这些共表达的效应 T 细胞可能会显著促进 pSS 中的持续免疫反应。
