Aspirin-treated human DCs up-regulate ILT-3 and induce hyporesponsiveness and regulatory activity in responder T cells
Aspirin-treated human DCs up-regulate ILT-3 and induce hyporesponsiveness and regulatory activity in responder T cells
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DOI：
10.1111/j.1600-6143.2006.01450.x
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发表时间：
2006-09-01
影响因子：
8.8
通讯作者：
Lombardi, G.
中科院分区：
文献类型：
--
作者：
Buckland, M.;Jago, C. B.;Lombardi, G.
成熟树突状细胞（mDC）是有效的抗原呈递细胞，但未成熟DC（iDC）已显示具有降低的抗原刺激能力。已经研究了不同的策略来增强树突状细胞（DC）的致耐受性能力。我们证明，在阿司匹林处理的人树突状细胞，有减少表达的CD 1a，HLA-DR和CD 86，上调ILT-3的表达和边缘增加PDL-1。阿司匹林处理的DC对成熟刺激（如脂多糖（LPS）或TNF α、IL-1 α和PGE）后的表型变化具有部分抗性（2）。阿司匹林处理的DC表现出正常的内吞功能，但具有降低的刺激同种异体T细胞的能力，这与iDC相当。此外，它们在应答者幼稚和记忆T细胞中诱导低应答性和调节活性;对于幼稚T细胞，这比iDC更快速和有效地实现。我们研究了这种调节活性的机制，发现细胞-细胞接触和抑制性细胞因子活性都参与其中，尽管没有一种细胞因子占主导地位。阻断ILT-3或IL-12不会降低这些DC诱导调节性T细胞上的调节或Foxp 3表达的能力。结果表明，阿司匹林处理的树突状细胞显示耐受性的潜力，这是感兴趣的，在减少慢性移植排斥反应的治疗潜力。
Mature dendritic cells (mDCs) are potent antigen presenting cells, but immature DCs (iDCs) have been shown to have reduced antigen stimulatory capacity. Different strategies have been investigated to augment the tolerogenic capacity of dendritic cells (DCs). We demonstrate that in aspirin-treated human DCs, there is reduced expression of CD1a, HLA-DR and CD86, up-regulation of ILT-3 expression and marginal increases in PDL-1. Aspirin-treated DCs are partially resistant to phenotypic changes following maturational stimuli, such as lipopolysaccharide (LPS) or TNF alpha, IL-1 alpha and PGE(2). Aspirin-treated DCs demonstrate normal endocytic function, but have a reduced ability to stimulate allogeneic T cells, which is comparable to iDCs. Furthermore, they induce hyporesponsiveness and regulatory activity in responder naive and memory T cells; for naive T cells this is achieved more quickly and efficiently than with iDCs. We investigated the mechanism of this regulatory activity and found that both cell-cell contact and inhibitory cytokine activity are involved, although no one cytokine predominates in importance. Blocking ILT-3 or IL-12 does not diminish the capacity of these DCs to induce regulation or Foxp3 expression on the regulatory T cells. Results demonstrate that aspirin-treated DCs display tolerogenic potential, which is of interest in their therapeutic potential in reducing chronic allograft rejection.