IL-4-producing CD4+ T cells in reactive lymph nodes during helminth infection are T follicular helper cells.

IL-4-producing CD4+ T cells in reactive lymph nodes during helminth infection are T follicular helper cells.
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DOI:
10.1084/jem.20090313
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发表时间:
2009-05-11
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Mohrs M
Mohrs M
中科院分区:
其他
文献类型:
--
作者:
King IL;Mohrs M

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白细胞介素(IL)-4是典型的T辅助型2 (Th2)细胞因子,由CD4+ T细胞在响应蠕虫感染时产生。IL-4不仅促进Th2细胞的分化,而且对免疫球蛋白(Ig) G1和IgE同型转换抗体应答也至关重要。尽管在Th2细胞和B淋巴细胞之间存在il -4介导的联系,但产生il -4的T细胞在淋巴结中的位置目前尚不清楚。使用IL-4双报告小鼠,我们检测了肠线虫感染时肠系膜引流淋巴结中Th2的反应和IL-4的产生。我们发现,虽然在整个B细胞和T细胞区域都发现了il -4 -表达的Th2细胞,但产生il -4的Th2细胞仅限于B细胞滤泡,并与生发中心相关。与其定位一致,IL-4产生者表达高水平的CXCR5、ICOS、PD-1、IL-21和BCL-6,这是T滤泡辅助细胞(Tfh)的表型特征。虽然IL-4在Th2和Tfh细胞的产生中是不可缺少的,但它的缺失导致B细胞扩增和成熟缺陷。我们的报告揭示了感染期间淋巴结中Th2启动和IL-4产生的区隔化,并确定Tfh细胞是体内IL-4的主要来源。
Interleukin (IL)-4 is the quintessential T helper type 2 (Th2) cytokine produced by CD4+ T cells in response to helminth infection. IL-4 not only promotes the differentiation of Th2 cells but is also critical for immunoglobulin (Ig) G1 and IgE isotype-switched antibody responses. Despite the IL-4–mediated link between Th2 cells and B lymphocytes, the location of IL-4–producing T cells in the lymph nodes is currently unclear. Using IL-4 dual reporter mice, we examined the Th2 response and IL-4 production in the draining mesenteric lymph nodes during infection with the enteric nematode Heligmosomoides polygyrus. We show that although IL-4–competent Th2 cells are found throughout the B and T cell areas, IL-4–producing Th2 cells are restricted to the B cell follicles and associate with germinal centers. Consistent with their localization, IL-4 producers express high levels of CXCR5, ICOS, PD-1, IL-21, and BCL-6, a phenotype characteristic of T follicular helper (Tfh) cells. Although IL-4 was dispensable for the generation of Th2 and Tfh cells, its deletion resulted in defective B cell expansion and maturation. Our report reveals the compartmentalization of Th2 priming and IL-4 production in the lymph nodes during infection, and identifies Tfh cells as the dominant source of IL-4 in vivo.
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