Kopitar A N, Ihan Hren N, Ihan A
Institute for Microbiology and Immunology, Medical Faculty Ljubljana, Slovenia.
Oral Microbiol Immunol. 2006 Feb;21(1):1-5. doi: 10.1111/j.1399-302X.2005.00237.x.
In various immunopathologic conditions, bacterial flora induce an immune response which results in inflammatory manifestations, e.g. periapical granuloma. Dendritic cells provide the main orchestration of specific immune responses. The aim of our study was to test the capacity of distinct oral bacterial antigens (prepared from Streptococcus mitis, Propionibacterium acnes, and Bacteroides spp.) to prime human dendritic cells for stimulation of the T-lymphocyte response. To assess the T-lymphocyte response, the expression of CD25, CD69, intracellular interferon gamma (cIFN-gamma), and intracellular interleukin 4 (cIL-4) was determined. Dendritic cells were prepared from leukocyte buffy coat from healthy blood donors. Monocytes were stimulated with IL-4 and GM-CSF and dendritic cells activated with bacterial lysates. Cell suspensions contained up to 90% dendritic cells, which represented 2-12% of the initial number of mononuclear cells. Lymphocyte subsets that developed in lymphocyte cultures after 1 week of stimulation were analyzed by flow cytometry. Dendritic cells, primed with antigens of Bacteroides fragilis have shown significantly higher activation and expression of intercellular IFN-gamma by T lymphocytes compared to negative controls. The dendritic cells primed with antigens of P. acnes had no effect on T-lymphocyte activation or cytokine production; instead they induced differentiation of T lymphocytes into CD25bright cells (regulatory T cells) with a potentially inhibitory effect on immune response. Dendritic cells primed with antigens of S. mitis induced increased expression of cIL-4. We conclude that commensal oral bacteria antigens prepared from B. fragilis, S. mitis, and P. acnes prime human dendritic cells to induce Th1, Th2, and T(reg) differentiation, respectively. This may advance our understanding of immunopathologic manifestations in the oral cavity and offer new possibilities for redirecting immune responses in mucosal vaccination.
在各种免疫病理状态下，细菌菌群会引发免疫反应，进而导致炎症表现，如根尖周肉芽肿。树突状细胞在特异性免疫反应中起主要调控作用。我们研究的目的是测试不同口腔细菌抗原（由缓症链球菌、痤疮丙酸杆菌和拟杆菌属制备）激活人树突状细胞以刺激T淋巴细胞反应的能力。为评估T淋巴细胞反应，我们测定了CD25、CD69、细胞内干扰素γ（cIFN-γ）和细胞内白细胞介素4（cIL-4）的表达。树突状细胞从健康献血者的白细胞层中制备。单核细胞用IL-4和GM-CSF刺激，树突状细胞用细菌裂解物激活。细胞悬液中树突状细胞含量高达90%，占初始单核细胞数量的2%-12%。刺激1周后，通过流式细胞术分析淋巴细胞培养物中产生的淋巴细胞亚群。与阴性对照相比，用脆弱拟杆菌抗原激活的树突状细胞显示T淋巴细胞的活化和细胞内IFN-γ表达显著更高。用痤疮丙酸杆菌抗原激活的树突状细胞对T淋巴细胞活化或细胞因子产生没有影响；相反，它们诱导T淋巴细胞分化为CD25bright细胞（调节性T细胞），对免疫反应可能具有抑制作用。用缓症链球菌抗原激活的树突状细胞诱导cIL-4表达增加。我们得出结论，由脆弱拟杆菌、缓症链球菌和痤疮丙酸杆菌制备的共生口腔细菌抗原分别激活人树突状细胞，诱导Th1、Th2和T(reg)分化。这可能会增进我们对口腔免疫病理表现的理解，并为黏膜疫苗接种中重定向免疫反应提供新的可能性。
