Analysis of Mechanism for Specific Immune Response Induction to Periodontopathic Bacteria

最初的免疫反应是由树突状细胞(DC)启动的，树突状细胞向幼稚的Th细胞通报入侵的病原体。DC在牙周非淋巴组织中以间质DC和朗格汉斯细胞的形式存在。这些外周DC在炎症部位捕获和处理抗原，然后迁移到淋巴结以启动Th细胞。DC在入侵细菌的刺激下经历了一系列不可逆的成熟过程，并以不同的动力学方式上调细胞因子的产生和表面分子的表达。为了探讨DC在牙周感染中的反应，我们分析了(1)CD40对人白细胞弹性蛋白酶(HLE)消化DC的敏感性，(2)细菌内毒素和牙龈假单胞菌菌毛对DC表型的影响。DC表面的CD40分子对HLE耐受，与人牙龈成纤维细胞分子不同，提示DC在PMNL渗入后可刺激局部免疫反应。此外，牙龈假单胞菌L…更多的PS和菌毛优先上调未成熟的PBDC上CD14和CD16的表达(CD14^-CD16^-)，尽管大肠杆菌内毒素不改变这些分子的表达。牙龈假单胞菌诱导的CD14~+CD16~+细胞强烈表达树突状细胞标志CD1a和HLA-DR，CD54高表达。但CD40、CD80、CD83、CD86的表达均低于内毒素刺激的DC，提示这些细胞处于免疫刺激活性较弱的DC中。牙龈假单胞菌对DC产生IL-6、IL-8、IL-10、IL-12和RANTES的刺激作用较弱。虽然牙龈假单胞菌诱导的同种异体T细胞增殖较弱，但两种脂多糖刺激的DC对右旋糖苷-FITC的摄取相似。这些结果提示牙龈假单胞菌和菌毛可触发DC的成熟，具有独特的特性，可调节牙周感染部位的免疫反应。牙龈假单胞菌诱导的CD14~+CD16~+DC亚群可能参与慢性炎症的诱导。较少

Primary immune responses are initiated by dendritic cells (DC), which inform naive Th cells about invading pathogens. DC settle as interstitial DC and Langerhans cells in peripheral non-lymphoid tissues including gingiva. These peripheral DC capture and process Ag at the site of inflammation, and then migrate to lymph nodes to prime Th cells. DC undergo a series of events leading to irreversible maturation upon stimulation with invading bacteria, and up-regulate cytokine production and surface molecule expression with different kinetics. To investigate the responses DC during periodontal infection, we analyzed(1)the sensitivitly to Human Leukocyte Elastase (HLE) digestion of CD40 on DC,(2)the effects of LPS and fimbriae from P. gingivalis on the phenotype of human in DC. CD40 on DC was resistant to HLE treatment, unlike the molecule of human gingival fibroblasts, suggesting that DC were capale to stimulate the local immune responses after PMNL infiltration. Furthermore, P. gingivalis L … More PS and fimbriae preferentially up-regulated CD14 and CD16 expression on immature PBDC (CD14^-CD16^-), although E. coli LPS did not alter the expression of these molecules. P. gingivalis LPS-induced CD14^+CD16^+ cells strongly expressed dendritic cell markers: Cdla and HLA-DR, and CD54 was highly expressed. However, CD40, CD80, CD83, CD86 expression was lower than E.coli LPS-stimulated DC, suggesting these cells were in DC with weak immunnostimulatory activity. P.gingivalis LPS was a weaker stimulator in terms of IL-6, IL-8, IL-10, IL-12, and RANTES production from DC as compared to E.coli LPS. Both LPS stimulated-DC induced comparable up-take of dextran-FITC, although P.gingivalis induced the statistically weaker allogenic T cell proliferation. These results suggestively indicated P. gingivalis LPS and fimbriae trigger a maturation of DC with unique characteristics, that modulate immune responses occurred at the site of periodontal infection. P.gingivalis-induced CD14^+CD16^+DC subsets may contribute to induction of chronic inflammation. Less