Steady-state migrating intestinal dendritic cells induce potent inflammatory responses in naive CD4+ T cells.
Steady-state migrating intestinal dendritic cells induce potent inflammatory responses in naive CD4+ T cells.
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稳态迁移肠道树突状细胞在幼稚 CD4 T 细胞中诱导强效炎症反应。
DOI：
10.1038/mi.2008.71
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发表时间：
2009
影响因子：
8
通讯作者：
Milling SW
中科院分区：
文献类型：
--
作者：
Milling SW
从肠道在淋巴中迁移的稳态树突状细胞 (DC) 会诱导对无害肠道抗原的耐受性，从而防止炎症反应。为了确定此类 DC 是否具有固有耐受性，我们在肠系膜淋巴结切除术后通过对大鼠胸导管插管来收集肠淋巴 DC（L-DC），并检查它们在同种异体混合白细胞反应中激活幼稚 CD4+ 淋巴细胞的能力。 L-DC 刺激强烈的增殖反应，诱导包括干扰素-γ 在内的炎性细胞因子的分泌，并诱导 FoxP3 阳性淋巴细胞分裂。为了确定激活的 CD4+ T 细胞是否已耐受，将它们休息并用受辐射的脾细胞重新刺激。重新刺激的 CD4+ T 细胞再次增殖并分泌炎症细胞因子。这些数据表明，在稳定状态下从肠道迁移的 DC 能够诱导初始 T 细胞产生强烈的炎症反应，尽管它们在维持口服耐受方面发挥着作用。
Steady-state dendritic cells (DCs) migrating in the lymph from the intestine induce tolerance to harmless intestinal antigens, preventing inflammatory responses. To determine if such DCs are inherently tolerogenic we collected intestinal lymph DCs (L-DCs) by cannulation of the thoracic duct of rats after mesenteric lymphadenectomy, and examined their capacity to activate naive CD4+ lymphocytes in an allogeneic mixed leucocyte reaction. L-DCs stimulated strong proliferative responses, induced secretion of inflammatory cytokines including interferon-γ, and induced FoxP3-positive lymphocytes to divide. To determine if the activated CD4+ T cells had been tolerized, they were rested and restimulated with irradiated splenocytes. The restimulated CD4+ T cells again proliferated and secreted inflammatory cytokines. These data demonstrate that the DCs, which migrate from the intestine in the steady state, are paradoxically able to induce strong inflammatory responses from naive T cells, despite their role in the maintenance of oral tolerance.