Expansion of circulating extrafollicular helper T-like cells in patients with chronic graft-versus-host disease
Expansion of circulating extrafollicular helper T-like cells in patients with chronic graft-versus-host disease
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慢性移植物抗宿主病患者循环滤泡外辅助 T 样细胞的扩增
DOI：
10.1016/j.jaut.2019.03.006
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发表时间：
2019-06-01
影响因子：
12.8
通讯作者：
Liu, Qifa
中科院分区：
文献类型：
--
作者：
Jin, Hua;Yang, Kaibo;Liu, Qifa
慢性移植物抗宿主病（cGVHD）是异基因造血干细胞移植（allo-HSCT）后发病和死亡的主要原因。已有研究表明，滤泡辅助性T细胞（Tfh）参与了cGVHD的免疫病理过程，但滤泡外辅助性T细胞在cGVHD发病过程中的作用尚不清楚。在本研究中，我们鉴定了人外周血中循环的滤泡外辅助性T样细胞（CD 44（hi）CD 62（lo）PSGL-1（lo）CD 4（+），c-滤泡外Th样）。我们对80例异基因造血干细胞移植后的c-滤泡外Th样细胞进行了表型和功能分析，以探讨这些细胞在人类cGVHD发展中的作用。活动性cGVHD患者的c-滤泡外Th样细胞的频率和计数显著高于无cGVHD的患者。中、重度cGVHD患者的c-滤泡外Th样细胞扩增较轻度cGVHD患者更为显著。与无cGVHD的患者相比，活动性cGVHD患者的C-滤泡外Th样细胞表现出诱导浆母细胞分化和IgG 1分泌的功能能力增加。此外，c-滤泡外Th样细胞水平与自身反应性B细胞、浆母细胞和IgG 1抗体的产生高度相关。我们的研究为人类cGVHD的发病机制提供了新的见解，并确定了c-滤泡外Th样细胞作为人类cGVHD发展的关键因素。
Chronic graft-versus-host disease (cGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies have shown that T follicular helper cells (Tfh) contribute to immune pathology in cGVHD, but the function of extrafollicular helper T cells during cGVHD pathogenesis remains largely unknown. In the current study, we identified circulating extrafollicular helper T-like cells (CD44(hi)CD62(lo)PSGL-1(lo)CD4(+), c-extrafollicular Th-like) in human peripheral blood. We performed phenotypic and functional analyses of c-extrafollicular Th-like cells from 80 patients after allo-HSCT to explore the role of these cells in the development of human cGVHD. Patients with active cGVHD had significantly higher frequencies and counts of c-extrafollicular Th-like cells than those of patients without cGVHD. The expansion of c-extrafollicular Th-like cells was more significant in patients with moderate/severe cGVHD than that of patients with mild cGVHD. C-extrafollicular Th-like cells from patients with active cGVHD exhibited increased functional abilities to induce plasmablast differentiation and IgG1 secretion compared to those of patients without cGVHD. Moreover, c-extrafollicular Th-like cell levels were highly correlated with the generation of autoreactive B cells, plasmablasts and IgG1 antibodies. Our studies provide new insights into human cGVHD pathogenesis and identify c-extrafollicular Th-like cells as a key element in the development of human cGVHD.