Bone marrow retaining colitogenic CD4+ T cells may be a pathogenic reservoir for chronic colitis
Bone marrow retaining colitogenic CD4+ T cells may be a pathogenic reservoir for chronic colitis
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DOI：
10.1053/j.gastro.2006.10.035
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发表时间：
2007-01-01
期刊：
影响因子：
29.4
通讯作者：
Watanabe, Mamoru
中科院分区：
文献类型：
--
作者：
Nemoto, Yasuhiro;Kanai, Takanori;Watanabe, Mamoru
背景与目的：虽然骨髓（BM）被认为是一种原发性淋巴器官，但它也被认为是记忆T细胞的避风港，这表明骨髓是记忆T细胞迁移和/或选择性保留的首选场所。我们在此报告了小鼠结肠炎模型中结肠炎源性BM CD4（+）记忆T细胞的存在及其诱导结肠炎的潜在能力。方法：将CD4(+)CD45RB（高）T细胞过继转移诱导的结肠炎严重联合免疫缺陷小鼠的BM CD4(+) T细胞与自发性结肠炎的结肠炎白介素(IL)-10（-/-）小鼠的BM CD4(+) T细胞分离，分析其表面表型、细胞因子的产生及诱导结肠炎的潜在活性。此外，我们评估了IL-7在维持结肠炎BM CD4(+) T细胞中的作用。结果：在结肠炎严重联合免疫缺陷小鼠和患病IL-10（-/-）小鼠的BM中存在大量CD4(+) T细胞，它们以il -7依赖的方式诱导1型T辅助物介导的结肠炎。这些常驻BM CD4(+) T细胞具有效应记忆(T- em; CD44（高）CD62L（-)IL-7R（高））表型，并优先附着于产生il -7的BM细胞。此外，在用结肠炎固有层CD4 + TEM细胞重组的il -7缺陷受体中，BM CD4(+) T-EM细胞的积累显著减少。结论：总的来说，这些发现表明，结肠炎小鼠中保留bm的结肠炎原性CD4（+）记忆T细胞作为持续终身结肠炎的储存库起着关键作用。
Background & Aims: Although bone marrow (BM) is known as a primary lymphoid organ, it also is known to harbor memory T cells, suggesting that this compartment is a preferential site for migration and/or selective retention of memory T cells. We here report the existence and the potential ability to induce colitis of the colitogenic BM CD4(+) memory T cells in murine colitis models. Methods: We isolated BM CD4(+) T cells obtained from colitic severe combined immunodeficient mice induced by the adoptive transfer of CD4(+)CD45RB(high) T cells and colitic interleukin (IL)-10(-/-) mice that develop colitis spontaneously, and analyzed the surface phenotype, cytokine production, and potential activity to induce colitis. Furthermore, we assessed the role of IL-7 to maintain the colitogenic BM CD4(+) T cells. Results: A high number of CD4(+) T cells reside in the BM of colitic severe combined immunodeficient mice and diseased IL-10(-/-) mice, and they retain significant potential to induce type-1 T helper-mediated colitis in an IL-7-dependent manner. These resident BM CD4(+) T cells have an effector memory (T-EM; CD44(high)CD62L(-)IL-7R(high)) phenotype and preferentially are attached to IL-7-producing BM cells. Furthermore, the accumulation of BM CD4(+) T-EM cells was decreased significantly in IL-7-deficient recipients reconstituted with the colitogenic lamina propria CD4(+) TEM cells. Conclusions: Collectively, these findings suggest that BM-retaining colitogenic CD4(+) memory T cells in colitic mice play a critical role as a reservoir for persisting lifelong colitis.