Foxp3-expressing CD103+ regulatory T cells accumulate in dendritic cell aggregates of the colonic mucosa in murine transfer colitis
Foxp3-expressing CD103+ regulatory T cells accumulate in dendritic cell aggregates of the colonic mucosa in murine transfer colitis
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DOI：
10.2353/ajpath.2006.050228
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发表时间：
2006-06-01
影响因子：
6
通讯作者：
Reimann, Joerg
中科院分区：
文献类型：
--
作者：
Leithaeuser, Frank;Meinhardt-Krajina, Tamara;Reimann, Joerg
在小鼠转移性结肠炎模型中，结肠炎形成或调节性t细胞反应的解剖区隔性知之甚少。因此，我们分析了大肠树突状细胞（DC）聚集体的假定功能，供体CD4(+) T细胞在结肠炎出现之前选择性地返回。共刺激分子MHC-II、CD40、CD80和CD86在DC聚集体中表达。在疾病的各个阶段，IL-23在DC聚集物中主要缺失，但在严重炎症的固有层中高水平表达。在疾病的早期和晚期，干扰素- γ在固有层中上调，而在DC聚集体中，它仅在完全发展的结肠炎中被检测到。相比之下，调节性T细胞的标记物Foxp3在T细胞转移过程中以DC聚集体表达，与这些聚集体中CD103(+) CD25(-) T细胞的出现一致。Foxp3在从患病小鼠固有层分离的CD103’t细胞中富集。缺乏CD103(+) T细胞的T细胞移植物与未分离的T细胞产生相似数量的结肠CD103(+) T细胞。我们得出结论，DC聚集体是参与表达CD103(+) CD25(-) CD4(+) foxp3的调节性T细胞扩增和/或分化的结构。
Little is known of the anatomical compartmentalization of colitogenic or regulatory T-cell responses in the murine transfer colitis model. Therefore, we analyzed the putative function of large intestinal dendritic cell (DC) aggregates, to which donor CD4(+) T cells selectively home before colitis becomes manifest. The co-stimulatory molecules MHC-II, CD40, CD80, and CD86 were expressed in DC aggregates. IL-23 was primarily absent from DC aggregates at an stages of disease but was expressed at high levels in the severely inflamed lamina propria. Interferon-gamma was up-regulated in the lamina propria during early and advanced disease, whereas in DC aggregates it was detectable to a significant degree only in fully developed colitis. in contrast, Foxp3, a marker of regulatory T cells, was expressed in DC aggregates on T-cell transfer, coinciding with the appearance of CD103(+) CD25(-) T cells in these clusters. Foxp3 was enriched in the CD103' T-cell fraction isolated from the lamina propria of diseased mice. T-cell grafts depleted of CD103(+) T cells generated similar numbers of colonic CD103(+) T cells as unfractionated T cells. We conclude that DC aggregates are structures involved in the expansion and/or differentiation of CD103(+) CD25(-) CD4(+) Foxp3-expressing regulatory T cells.