Colić Miodrag, Lukić Aleksandra, Vucević Dragana, Milosavljević Petar, Majstorović Ivana, Marjanović Marjan, Dimitrijević Jovan
Institute for Medical Research, Military Medical Academy, Belgrade, Serbia and Montenegro.
Arch Oral Biol. 2006 Dec;51(12):1120-30. doi: 10.1016/j.archoralbio.2006.05.003. Epub 2006 Jun 23.
The development and progression of periapical dental lesions, mediated by the specific immune response, are poorly understood. In these processes, an interplay of different proinflammatory and immunoregulatory cytokines is of crucial importance.
To examine the activation of T helper 1 (Th1) and Th2 immune responses in 25 human periapical lesions based on the ex vivo production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) by mononuclear cells (PL-MNC).
The levels of IFN-gamma and IL-4 in culture supernatants of PL-MNC, determined by ELISA, were correlated with concentrations of these cytokines in cultures of control MNC from peripheral blood (PB-MNC), cellular composition of inflammatory cells and phenotypic characteristics of PL-MNC.
We detected high levels of IFN-gamma in all samples, after cell stimulation with phorbol myristate acetate and Ca(2+) ionophore, that were not statistically different from the levels of IFN-gamma in PB-MNC cultures. IL-4 was detected in 76% samples, but its concentrations were much lower than in PB-MNC samples. The levels of IFN-gamma were higher in cultures of PL-MNC isolated from periapical lesions with predominance of T cells (T-type lesions) and correlated positively with the proportion of antigen-presenting cells (macrophages and dendritic cells), CD4(+) T cells and IgG2(+) B cells/plasma cells. The levels of IL-4 correlated negatively with the proportion of macrophages, but positively with the number of mast cells and IgG4(+) cells. IL-18Ralpha, a stable marker of Th1 cells, was detected on a relatively small proportion of CD3(+) T cells and its expression correlated with the levels of IFN-gamma. However, the expression of ST2L, a stable Th2 cell marker, was not detected. The levels of Th1 and Th2 cytokines did not correlate with clinical characteristics of the lesions, defined by the presence of symptoms.
Cumulatively, our results suggest the predominance of Th1 immune response in periapical lesions.
根尖周牙病变由特异性免疫反应介导，其发展和进程目前了解甚少。在这些过程中，不同促炎细胞因子和免疫调节细胞因子之间的相互作用至关重要。
基于单核细胞（PL-MNC）体外产生的干扰素-γ（IFN-γ）和白细胞介素-4（IL-4），检测25例人类根尖周病变中辅助性T细胞1（Th1）和Th2免疫反应的激活情况。
通过酶联免疫吸附测定法（ELISA）测定PL-MNC培养上清液中IFN-γ和IL-4的水平，并将其与外周血对照单核细胞（PB-MNC）培养物中这些细胞因子的浓度、炎性细胞的细胞组成以及PL-MNC的表型特征相关联。
在用佛波酯肉豆蔻酸酯和钙离子载体刺激细胞后，我们在所有样本中均检测到高水平的IFN-γ，其与PB-MNC培养物中IFN-γ的水平无统计学差异。在76%的样本中检测到IL-4，但其浓度远低于PB-MNC样本。从以T细胞为主的根尖周病变中分离出的PL-MNC培养物中，IFN-γ水平较高（T型病变），且与抗原呈递细胞（巨噬细胞和树突状细胞）、CD4(+) T细胞和IgG2(+) B细胞/浆细胞的比例呈正相关。IL-4水平与巨噬细胞比例呈负相关，但与肥大细胞数量和IgG4(+)细胞数量呈正相关。在相对较小比例的CD3(+) T细胞上检测到Th1细胞的稳定标志物IL-18Ralpha，其表达与IFN-γ水平相关。然而，未检测到Th2细胞稳定标志物ST2L的表达。Th1和Th2细胞因子的水平与由症状定义的病变临床特征无关。
总体而言，我们的结果表明根尖周病变中Th1免疫反应占主导。
