Evidence that CD8+ dendritic cells enable the development of gammadelta T cells that modulate airway hyperresponsiveness.

Evidence that CD8+ dendritic cells enable the development of gammadelta T cells that modulate airway hyperresponsiveness.
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证据表明CD8+树突状细胞能够开发调节气道高反应性的γT细胞。

DOI:
10.4049/jimmunol.181.1.309
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发表时间:
2008-07-01
影响因子:
4.4
通讯作者:
Born, Willi K.
Born, Willi K.
中科院分区:
医学2区
文献类型:
--
作者:
Cook, Laura;Miyahara, Nobuaki;Jin, Niyun;Wands, J. M.;Taube, Christian;Roark, Christina L.;Potter, Terry A.;Gelfand, Erwin W.;O'Brien, Rebecca L.;Born, Willi K.

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气道高反应性 (AHR) 是哮喘和其他几种疾病的标志,可以通过 γδ T 细胞调节。在卵清蛋白致敏和攻击的小鼠中,AHR依赖于过敏原特异性αβT细胞,但Vγδ1+γδT细胞自发增强AHR,而气道攻击诱导后的Vγ4+γδT细胞抑制AHR。这些 γδ T 细胞调节剂的活性是非过敏原特异性的,并且它们如何发展尚不清楚。我们现在证明 CD8 对于 AHR 抑制性和增强性 γδ T 细胞的发育至关重要,尽管这两种类型都不需要表达 CD8 本身。两种细胞类型在脾脏中都会遇到表达 CD8 的非 T 细胞,并且它们在 CD8 阴性环境中的功能发育可以通过含有 CD8+ DC(但不含有 CD8+ T 细胞或 CD8− DC)的转移脾细胞制剂来恢复。我们的研究结果表明,淋巴组织中的 CD8+ DC 通过直接细胞接触促进了 γδ T 细胞发育的早期阶段。 DC 表达的 CD8 可能参与这种相互作用。
Airway hyperresponsiveness (AHR), a hallmark of asthma and several other diseases, can be modulated by γδ T cells. In mice sensitized and challenged with ovalbumin, AHR depends on allergen-specific αβ T cells, but Vγδ1+ γδ T cells spontaneously enhance AHR, whereas Vγ4+ γδ T cells after being induced by airway challenge suppress AHR. The activity of these γδ T cell modulators is allergen-nonspecific, and how they develop is unclear. We now show that CD8 is essential for the development of both the AHR-suppressor and enhancer γδ T cells although neither type needs to express CD8 itself. Both cell types encounter CD8-expressing non-T cells in the spleen, and their functional development in an otherwise CD8-negative environment can be restored with transferred spleen cell preparations containing CD8+ DC, but not CD8+ T cells or CD8− DC. Our findings suggest that CD8+ DC in the lymphoid tissues enable an early step in the development of γδ T cells, through direct cell-contact. DC-expressed CD8 might take part in this interaction.
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