Leithäuser Frank, Meinhardt-Krajina Tamara, Fink Kerstin, Wotschke Beate, Möller Peter, Reimann Jörg
Department of Pathology, University of Ulm, Albert Einstein Allee 11, 89081 Ulm, Germany.
Am J Pathol. 2006 Jun;168(6):1898-909. doi: 10.2353/ajpath.2006.050228.
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 all 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.
在小鼠移植性结肠炎模型中，关于致结肠炎或调节性T细胞反应的解剖学分区知之甚少。因此，我们分析了大肠树突状细胞（DC）聚集体的假定功能，在结肠炎显现之前，供体CD4 + T细胞会选择性归巢到这些聚集体。共刺激分子MHC-II、CD40、CD80和CD86在DC聚集体中表达。在疾病的所有阶段，DC聚集体中主要不存在IL-23，但在严重炎症的固有层中高表达。在疾病早期和晚期，干扰素-γ在固有层中上调，而在DC聚集体中，仅在完全发展的结肠炎中可检测到显著程度的干扰素-γ。相比之下，调节性T细胞的标志物Foxp3在T细胞转移时在DC聚集体中表达，与这些簇中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细胞部分中富集。耗尽CD103 + T细胞的T细胞移植物产生的结肠CD103 + T细胞数量与未分级的T细胞相似。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。
