Quigley Máire F, Gonzalez Veronica D, Granath Anna, Andersson Jan, Sandberg Johan K
Center for Infection Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Eur J Immunol. 2007 Dec;37(12):3352-62. doi: 10.1002/eji.200636746.
Naive and central memory CD8 T cells use CCR7 to recirculate through T cell zones of secondary lymphoid organs where they can encounter antigen. Here we describe a subset of human CD8 T cells expressing CXCR5 which enables homing in response to CXCL13 produced within B cell follicles. CXCR5+ CD8 T cells were found in tonsil B cell follicles, and isolated cells migrated towards CXCL13 in vitro. They expressed CD27, CD28, CD45RO, CD69, and were CD7low, and produced IFN-gamma and granzyme A but lacked perforin, a functional profile suggesting that these cells are early effector memory cells in the context of contemporary T cell differentiation models. Receptors important in the interaction with B cells, including CD70, OX40 and ICOS, were induced upon activation, and CXCR5+ CD8 T cells could to some extent support survival and IgG production in tonsil B cells. Furthermore, CXCR5+ CD8 T cells expressed CCR5 but no CCR7, suggesting a migration pattern distinct from that of follicular CD4 T cells. The finding that a subset of early effector memory CD8 T cells use CXCR5 to locate to B cell follicles indicates that MHC class I-restricted CD8 T cells are part of the follicular T cell population.
初始和中枢记忆性CD8 T细胞利用CCR7在次级淋巴器官的T细胞区循环,在那里它们能够遇到抗原。在此,我们描述了一类表达CXCR5的人类CD8 T细胞亚群,该亚群能够响应B细胞滤泡内产生的CXCL13进行归巢。在扁桃体B细胞滤泡中发现了CXCR5+ CD8 T细胞,并且分离出的细胞在体外会朝着CXCL13迁移。它们表达CD27、CD28、CD45RO、CD69,CD7表达水平低,能产生IFN-γ和颗粒酶A,但缺乏穿孔素,这种功能特征表明在当代T细胞分化模型中,这些细胞是早期效应记忆细胞。与B细胞相互作用中重要的受体,包括CD70、OX40和ICOS,在激活后被诱导表达,并且CXCR5+ CD8 T细胞在一定程度上能够支持扁桃体B细胞的存活和IgG产生。此外,CXCR5+ CD8 T细胞表达CCR5但不表达CCR7,这表明其迁移模式与滤泡性CD4 T细胞不同。早期效应记忆性CD8 T细胞亚群利用CXCR5定位到B细胞滤泡这一发现表明,MHC I类限制性CD8 T细胞是滤泡性T细胞群体的一部分。