Table_4_Human Lymphoid Stromal Cells Contribute to Polarization of Follicular T Cells Into IL-4 Secreting Cells.xlsx

Fibroblastic reticular cells (FRCs) are the specialized lymphoid stromal cells initially identified as triggering T-cell recruitment and dynamic motion in secondary lymphoid organs. Interestingly, FRCs also display antigen presentation capacities and support lymphocyte survival. CXCR5+CD4+ follicular T cells are important players of B-cell maturation and antibody response. Our study reported that in vitro-differentiated FRC-like cells enhanced the growth of the whole CXCR5+CD4+ T-cell compartment, while enhancing IL-4 secretion specifically by the PD1dimCXCR5+CD4+ cell subset, in a Notch- and ICAM1/LFA1-dependent manner. In addition, we revealed that in follicular lymphoma (FL) tissues, previously identified as enriched for PD1hiCXCR5hiCD4+ mature follicular helper T cells, PD1dimCXCR5+CD4+ T cells displayed an enrichment for Notch and integrin gene signatures, and a Notch and ICAM-1-dependent overexpression of IL-4 compared to their non-malignant counterparts. These findings suggest that the crosstalk between FRCs and CXCR5+PD1dimCD4+ T cells may contribute to the FL IL-4 rich environment, thus providing new insights in FL lymphomagenesis.

成纤维网状细胞（Fibroblastic reticular cells, FRCs）是一类特化的淋巴基质细胞，最初被发现可触发次级淋巴器官内T细胞的招募与动态运动。有趣的是，FRCs同时具备抗原呈递能力，并可支持淋巴细胞存活。CXCR5+CD4+滤泡性T细胞是B细胞成熟与抗体应答的重要调控者。本研究发现，体外分化的类FRC细胞可扩增整体CXCR5+CD4+ T细胞群，并以依赖Notch及ICAM1/LFA1的方式，特异性增强PD1dimCXCR5+CD4+细胞亚群的IL-4分泌。此外，我们在滤泡性淋巴瘤（Follicular lymphoma, FL）组织中揭示：此前被证实富含PD1hiCXCR5hiCD4+成熟滤泡辅助性T细胞的FL组织中，PD1dimCXCR5+CD4+ T细胞呈现出Notch与整合素基因特征的富集，且相较于其非恶性对应细胞群，该亚群的IL-4过表达依赖于Notch及ICAM-1。上述研究结果表明，FRCs与CXCR5+PD1dimCD4+ T细胞之间的细胞互作可能参与构建FL的高IL-4微环境，从而为FL的淋巴瘤发生机制提供了新的研究视角。