Immunoregulatory Mechanisms in Adult Periodontitis

根据外周血淋巴细胞自体混合淋巴细胞反应(AMLR)的反应性，我们将牙周炎患者分为两组：AMLR低的患者和AMLR正常的患者。流式细胞仪分析显示低AMLR患者外周血中CD45RA^+细胞比例低于正常AMLR患者。然而，两组间的CD4^+CD45RO^+T细胞的百分比并无统计学差异。相比之下，慢性炎症牙周组织中T细胞的CD45RO+T细胞比例高于PBL，提示活化的T细胞选择性地迁移到牙周病变中。然后，我们研究了T细胞与人牙龈成纤维细胞(HGF)之间黏附的分子基础，以揭示T细胞滞留在病变部位的机制。用抗细胞黏附分子的单抗阻断实验表明，vla与…结合更多的GRINS和CD44分子参与了这种异型细胞-细胞相互作用。此外，IL-1β、TNF-α或IFN-γ刺激可增加HGF与活化T细胞的结合能力，而LFA-1/ICAM-1途径在这些情况下起中心作用。此外，还证实了经IFNGamma处理的HGF调节T细胞的增殖反应。然后，我们检测了牙周炎患者的PBL对牙周病原体的反应性。测定牙周炎患者外周血淋巴细胞对牙龈卟啉单胞菌(P.g)菌毛的体外增殖反应，并建立T细胞系及其克隆。菌毛特异性抗体水平高的患者外周血中PBL明显增殖至菌毛，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细胞可能聚集到牙周病变中，在局部免疫调节中发挥重要作用。较少

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