Lung dendritic cells are stimulated by ultrafine particles and play a key role in particle adjuvant activity
Lung dendritic cells are stimulated by ultrafine particles and play a key role in particle adjuvant activity
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DOI：
10.1016/j.jaci.2008.01.010
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发表时间：
2008-05-01
影响因子：
14.2
通讯作者：
Pieters, Raymond
中科院分区：
文献类型：
--
作者：
de Haar, Colin;Kool, Mirjam;Pieters, Raymond
背景资料：目的：探讨树突状细胞（DC）和共刺激分子CD 80、CD 86在超细炭黑颗粒（CBP）致敏中的作用。方法：采用CFSE标记的DO11.10 CD 4细胞，经鼻内暴露于颗粒物和卵清蛋白（OVA）后，观察细胞增殖情况。接下来，研究了支气管周围淋巴结（PBLN）中髓样树突状细胞（mDC）和浆细胞样树突状细胞的频率及其CD 80和CD 86的表达。还研究了体外暴露于CBP后骨髓来源的mDC上共刺激分子的表达，并通过使用CD 80/CD 86缺陷小鼠或细胞毒性T淋巴细胞相关抗原4（CTLA 4）-IG体内评估了共刺激在CBP佐剂活性中的重要性。我们的数据显示，CBP加OVA引起DO11.10 CD 4细胞的增殖和PBLN中高水平的细胞因子产生。此外，CBP + OVA联合暴露增加了PBLN中mDC的数量和共刺激分子的表达。此外，CBPs在体外上调树突状细胞上的CD 80/CD 86分子的表达，这是必要的粒子佐剂在vivo effects.Conclusion：总之，这项研究表明，树突状细胞和共刺激粒子佐剂活性的重要性。此外，我们首次表明，CBPs也可以直接诱导树突状细胞的成熟。
Background: The adjuvant activity of air pollution particles on allergic airway sensitization is well known, but the cellular mechanisms underlying this adjuvant potential are not clear.Objective: We sough to study the role of dendritic cells and the costimulatory molecules CD80 and CD86 in the adjuvant activity of ultrafine carbon black particles (CBP). Methods: The proliferation of CFSE-labeled DO11.10 CD4 cells was studied after intranasal exposure to particles and ovalbumin (OVA). Next the frequency of myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells and their expression of CD80 and CD86 were studied in the peribronchial lymph nodes (PBLNs). The expression of costimulatory molecules was also studied on bone marrow-derived mDCs after exposure to CBPs in vitro, and the importance of costimulation in CBP adjuvant activity was assessed by using CD80/CD86-deficient mice or cytotoxic T lymphocyte-associated antigen 4 (CTLA4)-Ig in vivo.Results: Our data show that CBPs plus OVA caused proliferation of DO11.10 CD4 cells and high levels of cytokine production in the PBLNs. Furthermore, the combined CBP plus OVA exposure increased the number of mDCs and expression of costimulatory molecules in the PBLNs. In addition, CBPs upregulated the expression of CD80/CD86 molecules on dendritic cells in vitro, which are necessary for the particle adjuvant effects in vivo.Conclusion: Together this study shows the importance of dendritic cells and costimulation in particle adjuvant activity. Furthermore, we show for the first time that CBPs can also directly induce maturation of dendritic cells.