Immunoregulatory Mechanisms in Adult Periodontitis

根据外周血淋巴细胞（PBL）自身混合淋巴细胞反应（AMLR）的反应性，将牙周炎患者分为低AMLR组和正常AMLR组。流式细胞术分析显示，与正常amlr患者相比，低amlr患者CD4^+细胞（CD4^+CD45RA^+ T细胞）中CD45RA^+细胞的百分比较低。然而，CD4^+ CD45RO^+ T细胞百分比在两组间无统计学差异。相比之下，浸润到慢性炎症牙龈的T细胞CD4^+CD45RO^+ T细胞的比例高于PBL患者，这表明活化的T细胞选择性地迁移到牙周病变。然后，我们研究了T细胞与人牙龈成纤维细胞（HGF）粘附的分子基础，以揭示T细胞在病变部位滞留的机制。利用细胞粘附分子特异性单克隆抗体的阻断实验表明，VLA结合了更多的grin和CD44分子参与了这种异型细胞-细胞相互作用。此外，研究还表明，il -1 β、tnf - α或IFNgamma刺激可增加HGF与活化T细胞的结合能力，而LFA-1/ICAM-1通路在这些情况下起着核心作用。此外，研究还表明，ifngamma处理的HGF可以调节t细胞的增殖反应。然后我们检测了牙周炎患者的PBL对牙周病细菌的反应性。研究了牙周炎患者PBL对牙龈卟啉单胞菌（Porphyromonas gingivalis， P.g）菌毛的体外增殖反应，并建立了T细胞系及其克隆。来自高水平菌毛特异性抗体患者的PBL向菌毛显著增殖，提示牙周炎患者外周血中存在菌毛特异性T细胞。这些菌毛特异性T细胞可聚集到牙周病变处，在局部免疫调节中发挥重要作用。少

Based on the responsiveness of autologous mixed-lymphocyte reactions (AMLR) of peripheral blood lymphocytes (PBL), we categorized periodontitis patients into two groups (low-AMLR patients and normal AMLR patients). Flow cytometric analyzes revealed a lower percentage of CD45RA^+ cells in CD4^+ cells (CD4^+CD45RA^+ T cells) in the low-AMLR patients than those in normal-AMLR patients. However, the percentage of CD4^+ CD45RO^+ T cells was not statistically different between the groups. In contrast, T cells infiltrated into chronically inflamed gingiva demonstrated a higher percentage of CD4^+CD45RO^+ T cells than PBL in those patients, suggesting that activated T cells selectively migrated into periodontal lesions.We then examined molecular basis of the adherence between T cells and human gingival fibroblasts (HGF) to reveal the mechanisms of T cell retention in diseased sites. Blocking experiments utilizing monoclonal antibodies specific for cell adhesion molecules revealed that VLA inte … More grins and CD44 molecules were involved in this heterotypic cell-cell interaction. Furthermore, it was also demonstrated that stimulation with IL-1beta, TNF-alpha or IFNgamma increased the binding abilities of HGF to activated T cells and that LFA-1/ICAM-1 pathway playd central roles in those situations. Furthermore, it was also demonstrated that IFNgamma-treated HGF regulated T-cell proliferative responses.We then examined the responsiveness of PBL from periodontitis patients to periodontopathic bacteria. PBL from periodontitis patients were assessed the proliferative responses to Porphyromonas gingivalis (P.g) fimbriae in vitro and were subjected to the establishment of T cell lines and their clones. PBL from the patients with high level of fimbriae-specific antibodies significantly proliferated to the fimbriae, suggesting that fimbriae-specific T cells were present in the peripheral blood of periodontitis patients. These fimbriae-specific T cells may recruit to the periodontal lesions and play important roles in local immunomodulation. Less