The high expression level of programmed death-1 ligand 2 in oral lichen planus and the possible costimulatory effect on human T cells
The high expression level of programmed death-1 ligand 2 in oral lichen planus and the possible costimulatory effect on human T cells
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口腔扁平苔藓中程序性死亡1配体2的高表达及其对人T细胞可能的共刺激作用
DOI：
10.1111/j.1600-0714.2011.01035.x
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发表时间：
2011-08-01
影响因子：
3.3
通讯作者：
Tang, Guo-Yao
中科院分区：
文献类型：
--
作者：
Du, Guan-Huan;Qin, Xiao-Peng;Tang, Guo-Yao
背景：口腔扁平苔藓（OLP）是一种t细胞介导的慢性自身免疫性疾病，其确切病因尚不清楚。最近发现的共刺激程序性死亡-1 （PD-1）分子及其配体PD-L1和PD-L2已被鉴定为CD28-B7家族分子，并构成了免疫介导疾病的潜在治疗应用的调控途径。方法：应用免疫组织化学和实时荧光定量PCR技术检测两种PD-1配体在OLP患者局灶黏膜和外周血中蛋白和基因水平的表达。接下来，我们使用PD-L2。Ig融合蛋白，并观察其对T细胞的影响，T细胞与ifn - γ处理的角化细胞（KCs）在PHA存在下共培养。结果：我们发现，与正常人相比，OLP患者外周血和局部病变组织中PD-L2在基因和蛋白水平上的表达均有统计学差异。上述共培养模型上清液中T细胞的增殖能力和ifn - γ的表达水平均显著增强（P < 0.05）。PD-L2。Ig融合蛋白显著加重模型T细胞凋亡，抑制T细胞增殖，降低IL-2、ifn - γ释放水平（P < 0.05）。结论：PD-L2作为一种共刺激分子，其表达的增加可能对OLP体内局部免疫应答具有重要的调节作用。中华口腔医学杂志，2011,40:525-532
BACKGROUND: Oral lichen planus (OLP) is a T-cell-mediated chronic autoimmune disease whose precise etiology is unknown. The recently identified costimulatory programmed death-1 (PD-1) molecule and its ligands, PD-L1 and PD-L2, have been identified as CD28-B7 family molecules and constitute a regulatory pathway of potential therapeutic use in immune-mediated diseases.METHODS: We examined the expression of two ligands of PD-1 at both the protein and gene level in the focal mucosa and peripheral blood of OLP patients using immunohistochemistry and real-time PCR. Next, we used the PD-L2.Ig fusion protein and observed its effects on T cells, which were co-cultured with IFN-gamma-treated keratinocytes (KCs) in the presence of PHA.RESULTS: We found that the expression of PD-L2 at both the gene and protein level was statistically different in peripheral blood and local lesion tissue of patients with OLP compared to the normal controls. The proliferation ability of T cells and the expression level of IFN-gamma in the supernatant of the above co-culture model were significantly augmented (P < 0.05). PD-L2.Ig fusion protein significantly aggravated the apoptosis of T cells, inhibited the proliferation of T cells and decreased the release levels of IL-2 and IFN-gamma in the model (P < 0.05).CONCLUSION: These data show that the increased expression of PD-L2, as a costimulatory molecule, may have an important modulatory function on the local immune responses of OLP in vivo. J Oral Pathol Med (2011) 40: 525-532