The role of adhesion molecules and cytokines in chronic periodontitis

牙周炎是由病原菌激活的免疫活性细胞引起的慢性炎症。我们利用NK细胞株NK3.3研究了T细胞与成纤维细胞之间的相互作用，以及CD2刺激对IL-2介导的NK细胞增殖的共刺激作用，以及CD2和IL-2通过CD2和IL-2信号转导通路的作用。PHA激活的T细胞与ICAM-1和ECMs的黏附呈剂量依赖关系，PMA显著增强PHA激活的T细胞与ICAM和ECMs的黏附。CC趋化因子如MCP-1和RANTES可促进PHA激活的T细胞与ICAM-1的黏附，但不能促进其与ECM的黏附，而CX3C-趋化因子和Fractalkine对PHA激活的T细胞黏附无影响。为了研究T细胞与成纤维细胞相互作用的自然环境，检测了PHA激活的T细胞与固定化成纤维细胞样细胞系E11细胞的结合情况。我们发现PHA激活的T细胞与E11细胞的黏附依赖于ICAM-1，MCP-1和RANTES而不是Fractalkine促进了PHA激活的T细胞与E11细胞的结合。提示某些趋化因子在T细胞与成纤维细胞的黏附中起重要作用，可能通过增强炎症部位的免疫反应参与牙周炎的发病过程。CD2共刺激交联剂显著促进IL-2介导的NK3.3增殖。CD2的交联诱导蛋白酪氨酸激酶Syk和接头蛋白Shc和Cbl的酪氨酸磷酸化。然而，IL-2刺激增加了Shc的酪氨酸磷酸化，但对Syk和Cbl没有影响。Cb1通过N-SH3结构域与Grb2结构域结合，而Shc通过激活依赖的方式与Grb2到SH2结构域结合。

Periodontitis is chronic inflammation caused by immunocompetent cells activated by pathologic bacteria. We investigated the interaction between T cells and fibroblasts, and costimulatory effects of CD2 stimulation on IL-2-mediated NK cell proliferation and signal pathways through CD2 and IL-2 using NK cell line, NK3.3.PHA-activated T cells adhered to ICAM-1 and ECMs in a dose-dependent manner and PMA markedly enhanced the adhesion of PHA-activated T cells to ICAM and ECMs. The CC-chemokines, such as MCP-1 and RANTES, enhanced adhesion of PHA-activated T cells to ICAM-1, but not to ECMs, whereas, the CX3C-chemokine, fractalkine had no effect on PHA-activated T cell adhesion. To examine the natural setting of the interaction between T cells and fibroblasts, the binding of PHA-activated T cells to immobilized fibroblast like cell line, E11 cells was examined. We found that adhesion of PHA-activated T cells to E11 cells was ICAM-1 dependent and that MCP-1 and RANTES, but not fractalkine, enhanced binding of PHA-activated T cells to E11 cells. These results suggest that some chemokines have important roles in adhesion of T cells to fibroblasts, which may be involved in pathogenesis of periodontitis through enhancing immunologic reaction at the inflammatory sites.Costimulation of CD2 crosslinking significantly enhanced IL-2-mediated NK3.3 proliferation. Crosslinking of CD2 induced tyrosine phosphorylation of protein tyrosine kinase, Syk and adapter proteins, Shc and Cbl. However, IL-2 stimulation enhanced tyrosine phosphorylation of Shc, but not Syk nor Cbl. Cbl constitutively associates with Grb2 through N-SH3 domain, whereas Shc associates with Grb2 through SH2 domain in an activation-dependent manner.