Alveolar epithelial type II cells induce T cell tolerance to specific antigen
Alveolar epithelial type II cells induce T cell tolerance to specific antigen
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DOI：
10.4049/jimmunol.180.2.881
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发表时间：
2008-01-15
影响因子：
4.4
通讯作者：
Wright, Jo Rae
中科院分区：
文献类型：
--
作者：
Lo, Bernice;Hansen, Soren;Wright, Jo Rae
肺部面临着免疫挑战，即在保持对无害的AGS耐受性的同时，迅速消除吸入的病原体。这种免疫平衡的破坏可能会导致肺部炎症性疾病，如过敏或哮喘。观察到肺泡上皮型H细胞(II型)结构性地表达II型MHC，使我们假设II型细胞在获得性免疫反应中发挥作用。由于II型细胞不表达可检测到的共刺激分子CD80和CD86，我们认为II型细胞抑制了初始T细胞的激活。纯化的小鼠II型细胞不能激活T细胞对特定的抗原或同种异体反应。尽管干扰素-γ治疗上调了II型MHC的表达，但它并没有改变II型细胞激活T细胞的能力。相反，II型细胞能够以一种依赖于Ag的方式抑制T细胞对特定抗原的后续激活。用II型细胞和抗原启动T细胞会导致T细胞被抑制而进一步激活，即使在从II型细胞中移除之后也是如此。因此，肺脏的II型细胞有助于T细胞对非致病环境AGS的耐受。
The lungs face the immunologic challenge of rapidly eliminating inhaled pathogens while maintaining tolerance to innocuous Ags. A break in this immune homeostasis may result in pulmonary inflammatory diseases, such as allergies or asthma. The observation that alveolar epithelial type H cells (Type II) constitutively express the class II MHC led us to hypothesize that Type II cells play a role in the adaptive immune response. Because Type II cells do not express detectable levels of the costimulatory molecules CD80 and CD86, we propose that Type II cells suppress activation of naive T cells. Purified murine Type II cells were unable to activate T cells to specific Ag or in an alloreactive assay. Although IFN-gamma treatment up-regulated class II MHC expression, it did not alter the ability of the Type II cells to activate T cells. Rather, the Type II cells were able to suppress T cells from subsequent activation to specific Ag in an Ag-dependent manner. Priming T cells with Type II cells and Ag resulted in T cells that were suppressed to further activation, even after removal from the Type II cells. Thus, Type II cells of the lung help tolerize T cells to nonpathogenic environmental Ags.