Lyme arthritis synovial γδ T cells instruct dendritic cells via Fas ligand
Lyme arthritis synovial γδ T cells instruct dendritic cells via Fas ligand
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DOI：
10.4049/jimmunol.175.9.5656
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发表时间：
2005-11-01
影响因子：
4.4
通讯作者：
Budd, RC
中科院分区：
文献类型：
--
作者：
Collins, C;Wolfe, J;Budd, RC
T细胞参与对多种感染性微生物的先天免疫反应。在免疫反应的早期阶段，当抗原特异性T细胞的频率很低时，它们还通过诱导树突状细胞(DC)成熟而与适应性免疫反应有关。我们观察到，在伯氏疏螺旋体存在的情况下，来自莱姆关节炎关节液的滑膜V-1T细胞可以有效地诱导DC成熟，包括产生IL-12，并增加CD40和CD86的表面表达。然后，激活的DC能够刺激V Delta 1T细胞上调CD25。这两个过程主要是由Fas刺激而不是CD40通过V delta1T细胞高表达Fas配体激活DC。DC对Fas诱导的死亡具有抵抗力，这是由于高水平表达Fas抑制因子c-flip所致。这种作用将Fas介导的信号从caspase级联转移到ERK、MAPK和NF-kappa B通路。这些发现肯定了在先天免疫反应的早期阶段，某些T细胞群体与DC相互作用的重要性。他们还强调了这样一种观点，即随着c-flip水平的增加，Fas信号可以从诱导细胞凋亡转向导致细胞效应器功能的途径。
gamma delta T cells participate in the innate immune response to a variety of infectious microorganisms. They also link to the adaptive immune response through their induction of maturation of dendritic cells (DC) during the early phase of an immune response when the frequency of Ag-specific T cells is very low. We observe that in the presence of Borrelia burgdorferi, synovial V delta 1 T cells from Lyme arthritis synovial fluid potently induce maturation of DC, including production of IL-12, and increased surface expression of CD40 and CD86. The activated DC are then able to stimulate the V delta 1 T cells to up-regulate CD25. Both of these processes are initiated primarily by Fas stimulation rather than CD40 activation of DC via high expression of Fas ligand by the V delta 1 T cells. DC are resistant to Fas-induced death due to expression of high levels of the Fas inhibitor c-FLIP. This effect serves to divert Fas-mediated signals from the caspase cascade to the ERK MAPK and NF-kappa B pathways. The findings affirm the importance of the interaction of certain T cell populations with DC during the early phases of the innate immune response. They also underscore the view that as levels of c-FLIP increase, Fas signaling can be diverted from induction of apoptosis to pathways leading to cell effector function.