A major population of mucosal memory CD4+ T cells, coexpressing IL-18Rα and DR3, display innate lymphocyte functionality.
A major population of mucosal memory CD4+ T cells, coexpressing IL-18Rα and DR3, display innate lymphocyte functionality.
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粘液组织含有大量的记忆性CD 4 + T细胞，其通过T细胞受体依赖性与抗原呈递细胞的相互作用，被认为在屏障防御和维持组织完整性中具有关键作用。在这里，我们确定了一个主要的记忆CD 4 + T细胞亚群在屏障表面，共表达白细胞介素-18受体α（IL-18 R α）和死亡受体-3（DR 3），并显示先天淋巴细胞功能。细胞因子IL-15或DR 3配体肿瘤坏死因子（TNF）样细胞因子1A（TL 1a）诱导记忆IL-18 R α+ DR 3 + CD 4 + T细胞产生干扰素-γ、TNF-α、IL-6、IL-5、IL-13、粒细胞-巨噬细胞集落刺激因子（GM-CSF），以及在IL-12/IL-18存在的情况下产生IL-22。TL 1a与IL-15协同作用以增强这种应答，同时抑制IL-15诱导的IL-10产生。TL 1a和IL-15介导的细胞因子诱导需要IL-18的存在，而IL-5、IL-13、GM-CSF和IL-22的诱导不依赖于IL-12。具有相似功能的IL-18 R α+ DR 3 + CD 4 + T细胞存在于人皮肤、鼻息肉，特别是肠道中，在慢性炎症中，它们与IL-18产生细胞一起定位于淋巴聚集体中。总的来说，这些结果表明，人记忆IL-18 R α+ DR 3 + CD 4 + T细胞可能有助于屏障表面的抗原非依赖性先天性应答。
Mucosal tissues contain large numbers of memory CD4+ T cells that, through T-cell receptor-dependent interactions with antigen-presenting cells, are believed to have a key role in barrier defense and maintenance of tissue integrity. Here we identify a major subset of memory CD4+ T cells at barrier surfaces that coexpress interleukin-18 receptor alpha (IL-18Rα) and death receptor-3 (DR3), and display innate lymphocyte functionality. The cytokines IL-15 or the DR3 ligand tumor necrosis factor (TNF)-like cytokine 1A (TL1a) induced memory IL-18Rα+DR3+CD4+ T cells to produce interferon-γ, TNF-α, IL-6, IL-5, IL-13, granulocyte–macrophage colony-stimulating factor (GM-CSF), and IL-22 in the presence of IL-12/IL-18. TL1a synergized with IL-15 to enhance this response, while suppressing IL-15-induced IL-10 production. TL1a- and IL-15-mediated cytokine induction required the presence of IL-18, whereas induction of IL-5, IL-13, GM-CSF, and IL-22 was IL-12 independent. IL-18Rα+DR3+CD4+ T cells with similar functionality were present in human skin, nasal polyps, and, in particular, the intestine, where in chronic inflammation they localized with IL-18-producing cells in lymphoid aggregates. Collectively, these results suggest that human memory IL-18Rα+DR3+ CD4+ T cells may contribute to antigen-independent innate responses at barrier surfaces.
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