转化生长因子β受体在口腔扁平苔藓CD8+T细胞中的表达

目的 研究转化生长因子β受体(transforming growth factor-β receptor,TGF-βR)在口腔扁平苔藓(oral lichen planus,OLP)组织中CD8+T细胞中的表达,探讨TGF-βR在OLP发病中的作用.方法 采用免疫组化双标记法检测28例OLP组织中CD8+T细胞TGF-βR Ⅰ和TGF-βR Ⅱ蛋白的表达.以10例临床正常口腔黏膜(normal oral mucosa,NOM)为对照组.结果 OLP组织中CD8+及TGF-βR Ⅰ、CD8+及TGF-βR Ⅱ双标记细胞的阳性率分别为(8.82±9.98)%、(1.11±2.94)%.NOM组织中双标记细胞均为零.OLP组CD8+T细胞中TGF-βRⅡ表达与NOM组相比差异无统计学意义(P＞0.05),TGF-βR Ⅰ与NOM组相比表达增强.结论 提示OLP组织CD8+T细胞存在TGF-β信号传导异常.这可能是CD8+T细胞缺乏有效抑制、致使OLP慢性炎性反应长期持续的因素之一.     

Smad 2/3、7蛋白在OLP CD8+T细胞中的表达

目的:观察Smad2/3、在口腔扁平苔藓(oral lichen planus,OLP)CD8 T细胞中的表达。方法:采用免疫7 组化双标记法检测28例OLP组织中CD8 T细胞Smad2/3、7蛋白表达水平。设10例临床正常口腔黏膜(Normal oral mucosa,)为对照组。结果:NOMNOM组织中CD8 /Smad2/3、CD8 /Smad7双标记阳性细胞均为零。OLP组织中, CD8/Smad2、3和CD8 /Smad7双标记细胞的阳性率分别为1.020 1.24,5.524±5.074。结论:与NOM相比, OLP组织中CD8 T细胞Smad2、 3表达无明显升高。而Smad7阳性颗粒均位于细胞浆中,可能部分阻碍了TGF-β/Smad正向反馈通路,从而引起CD8 T细胞抑制不足,造成OLP慢性炎症的长期持续。     

4-1BB、CD8在口腔扁平苔藓组织中的表达研究

目的 检测共刺激信号4-1BB及CD8在口腔扁平苔藓(oral lichen planus,OLP)组织中的表达,探讨OLP病损中4-1BB介导CD8⁺ T细胞免疫应答的潜在机制。方法 选取31例OLP患者(糜烂型15例、非糜烂型16例),15例健康成人(对照组)为研究对象,收集其临床及病理资料,采用免疫组织化学法检测局部组织中4-1BB、CD8的表达情况。结果 OLP患者局部组织中4-1BB及CD8的表达高于对照组(P<0.05),且两者表达呈正相关(r=0.389,P<0.05),糜烂型OLP患者中CD8、4-1BB表达高于非糜烂型(P<0.05)。在OLP不同的临床亚组中,VAS评分、REU评分及基底细胞损伤程度均表现出差异(P<0.05)。Spearman相关性分析结果显示,CD8与基底细胞损伤程度呈正比(P<0.05),CD8、4-1BB分别与VAS评分、REU评分存在正相关性(P<0.05)。结论 OLP患者局部组织中4-1BB表达升高,其与疾病活动进展程度呈正相关,4-1BB可能通过调控CD8⁺ T细胞参与OLP的发生发展。     

口腔黏膜癌前病变和口腔鳞癌组织Fas/FasL的表达及其意义

目的：研究调亡相关基因Fas／FasL在正常口腔黏膜、上皮异常增生和口腔鳞癌组织中的表达及意义。方法：应用免疫组织化学方法检测10例正常口腔黏膜、26例上皮异常增生、38例口腔鳞癌组织及肿瘤浸润淋巴细胞（TIL）中Fas／FasL的表达。结果：Fas在正常口腔黏膜中广泛表达;上皮异常增生和鳞癌组织表达明显下调（P〈0．05）;Fas表达与口腔鳞癌分化程度有关;FasL在正常口腔黏膜不表达;上皮异常增生和鳞癌组织表达明显上调（P〈0．05）;FasL表达与口腔鳞癌分化程度无关（P〉0．05）;TIL细胞Fas、FasL阳性表达率为81．6％和84．2％。结论：Fas表达与口腔黏膜上皮细胞的自然分化成熟、衰老及口腔鳞癌的形成和肿瘤的恶性度有关;FasL的表达上调可能是口腔鳞癌组织免疫反攻击的体现;Fas、FasL可作为监测口腔上皮癌变的标记物。     

老年牙周炎牙龈组织Fas/Apo-1(CD95)抗原表达的免疫组织化学研究

目的 :观察慢性老年牙周炎牙龈组织中Fas/Apo - 1(CD95 )抗原表达和分布情况。方法 :采用免疫组织化学染色方法对 10例慢性老年牙周炎患者、10例慢性成人牙周炎患者、10例青少年牙周炎患者和 10例健康老年人牙龈组织中Fas/Apo - 1(CD95 )抗原阳性表达和分布情况进行了观察和比较。结果 :在慢性老年牙周炎组完整的牙龈鳞状上皮间桥、核周胞浆Fas/Apo - 1(CD95 )抗原阳性表达和结缔组织中淋巴细胞Fas/Apo - 1(CD95 )抗原阳性表达为 4组中最强 ;健康老年人组上皮角化层Fas/Apo - 1(CD95 )抗原阳性表达为 4组中最强 ;慢性成人牙周炎组和青少年牙周炎组结缔组织中淋巴细胞和吞噬细胞Fas/Apo - 1(CD95 )抗原阳性表达强于健康老年人组 ;慢性老年牙周炎组上皮细胞和上皮细胞的细胞间桥Fas/Apo - 1(CD95 )抗原阳性表达例数明显高于慢性成人牙周炎组和青少年牙周炎组 (P <0 .0 5 ) ;健康老年人组结缔组织中淋巴细胞和吞噬细胞Fas/Apo - 1(CD95 )抗原阳性表达例数明显低于其它 3组 (P <0 .0 5 )。结论 :由于感染性炎症和衰老的影响 ,①牙周炎患者和健康老年人牙龈组织中鳞状上皮凋亡细胞发生部位与身体其他器官鳞状上皮细胞凋亡发生部位不同 ;②在慢性老年牙周炎患者牙龈组织中上皮细胞和炎性细胞对细胞凋亡易感性     

口腔扁平苔藓病损区B7抗原及CD28的表达及意义

目的 :探讨B7/CD2 8共刺激旁路在口腔扁平苔藓 (OLP)病损形成及发展中的作用。方法 :采用免疫组化方法对 46例OLP病损区B7抗原 (B7-1/CD80 ,B7-2 /CD86)及其配体CD2 8的表达情况进行检测 ,并与其局部病变、临床病程及病变类型相联系。结果 :①CD2 8阳性细胞见于所有OLP病损固有层淋巴细胞浸润带中 ,占总浸润细胞数的 45 % -80 %。②CD86低水平表达于正常口腔黏膜上皮及固有层的部分树突状细胞 ,但在不同病程及病变类型OLP病损中均有表达上调 (t =3 4.3 5 ,P <0 .0 1) ;CD86阳性细胞数在有基底层破坏的OLP病损中更多 ,差异有显著性 (t =2 .72 ,P <0 .0 5 )。③OLP病损中CD86阳性细胞与CD2 8阳性细胞之间存在数量上的正相关关系 (γ =0 .946,P <0 .0 1) ;④CD80 低水平表达于 80 .43 %的OLP病损上皮及邻近的结缔组织中 ,但在正常黏膜无表达。结论 :CD2 8-B7共刺激信号涉及OLP病损的形成及发展过程 ;其中 ,口腔黏膜上皮抗原呈递细胞上的CD86与存在于T细胞上的CD2 8分子间的结合及产生的效应 ,在OLP局部破坏性病损的形成中可能起重要作用 ,而CD80 则可能与OLP病损的慢性迁延状态有关。     

Fas配体在口腔鳞状细胞癌中的表达--一种免疫反攻模式的体现

目的 研究口腔鳞状细胞癌组织Fas配体(FasL)的表达及其临床病理学意义。方法 应用免疫组织化学方法检测10例正常口腔粘膜、38例口腔鳞癌组织及肿瘤浸润淋巴细胞(TIL)和11例转移淋巴结中FasL的表达情况。结果 FasL在正常口腔粘膜中不表达,在鳞癌组织中表达明显上调(P<0.05);FasL表达与口腔鳞癌分化程度无关(P>0.05);32/38例(84.2％)鳞癌组织TIL细胞FasL表达阳性;有淋巴结转移者FasL阳性表达率明显高于无转移者(P<0.05)。结论 FasL的上调表达是口腔鳞癌组织免疫反攻击的体现,对促进肿瘤的发生发展及转移有重要作用。     

Fas、FasL在Sj(o)gren综合征涎腺组织中的表达及意义

目的观察Sjogren综合征(Sjogren's syndrome,SS)涎腺组织和正常涎腺组织中凋亡相关蛋白Fas、FasL的表达情况,探讨SS涎腺组织中细胞凋亡的途径.方法采用SP免疫组织化学法,检测23例SS涎腺组织和16例正常涎腺组织中Fas、FasL的表达情况.结果在SS腺泡上皮细胞中,Fas、FasL的表达均高于正常组,有显著性差异(P＜0.005);两组导管上皮细胞中,Fas、FasL的表达均无显著性差异(P＞0.05).结论在SS涎腺组织中Fas、FasL的表达升高.SS涎腺上皮细胞在Fas/FasL介导下过度凋亡,造成了腺体结构的破坏和分泌功能的丧失.     

口腔黏膜癌前病变及鳞癌中Fas/FasL的表达研究

目的 :研究凋亡相关基因Fas/FasL在口腔正常粘膜、上皮单纯增生、上皮异常增生和鳞癌中的表达及意义。方法 :采用SABC免疫组织化学方法检测正常口腔粘膜 ( 10例 ) ,上皮单纯增生 ( 8例 ) ,上皮异常增生 ( 2 0例 ) ,鳞癌 ( 32例 )中Fas/FasL的表达。结果 :在正常口腔粘膜中Fas表达于棘层和粒层细胞的胞膜 ;FasL局限于基底层细胞的胞膜和胞浆。上皮异常增生中随异常增生程度的增高 ,Fas表达降低 ;FasL表达增强 ,甚至遍布上皮全层。鳞癌组中Fas表达明显低于正常组 (P <0 .0 5 ) ,且与组织学分级呈正相关 ;FasL表达明显高于正常组 (P <0 .0 5 ) ,且与组织学分级呈负相关。结论 :Fas在调节鳞状上皮细胞自我更新中具有重要作用。Fas表达水平下调 ,FasL上调 ,可能是口腔上皮癌变过程中的一个早期事件。Fas/FasL是肿瘤细胞逃逸肿瘤反应T细胞攻击而获得免疫赦免的重要机制之一。     

口腔异常增生上皮及鳞癌组织中Fas、FasL及Bcl-2的研究

目的:研究凋亡相关基因Fas、FasL及Bcl-2蛋白在口腔黏膜异常增生上皮及鳞癌组织中变化规律。方法:采用免疫组织化学SP法检测口腔黏膜异常增生上皮及鳞癌组织中凋亡相关基因Fas、FasL及Bcl-2蛋白表达。结果:发现Fas表达水平无差异,但Fas染色在正常、单纯性增生、轻度异常增生组织中以胞膜型为主,而原位癌及鳞癌组织中以胞浆型为主,中度异常增生时两型兼有;FasL在鳞癌组织中过度表达,与对照组、单纯增生组比较差异显著(P<0.05),FasL表达与局部浸润的淋巴细胞呈负相关(r=-0.437,P<0.05)。Bcl-2表达在原位癌时出现高峰,与对照组、单纯增生组比较差异显著(P<0.05),Bcl-2表达水平与Fas L表达水平相关显著(r=0.337,P<0.05)。结论:Fas、FasL及Bcl-2参与了口腔癌前病变癌变发生发展过程,作用的机制可能是它们分别或协同作用抑制细胞凋亡、延长异常细胞生存期、利于免疫逃逸,为细胞癌变提供了条件。     

Apoptosis in oral lichen planus

Apoptotic cell death may be a contributory cause of basal cell destruction in oral lichen planus (OLP). Therefore. the purpose of this study was to investigate the rate of apoptosis in OLP and the expression of two proteins (FasR and FasL) regulating this process. Biopsies from 18 patients with histologically diagnosed OLP were investigated, with comparison to normal oral mucosa of healthy persons. For visualisation of DNA fragmentation, the TUNEL method was used. In order to characterise the infiltrating cell population (CD3. CD4, CD8) and expression of FasR and FasL, we used an immunohistochemical technique. The results showed that T cells dominated in the subepithelial cell infiltrate. Within the epithelium the apoptotic cells were confined to the basal cell layer, and more apoptotic cells were seen in areas with basal cell degeneration and atrophic epithelium. There was a prominent expression of FasR/FasL in OLP. with a rather uniform distribution throughout the inflammatory cell infiltrate. In the epithelium, the FasR/FasL expression was more abundant in the basal cell area compared to the suprabasal cell layer. In conclusion, apoptosis within the epithelium is significantly increased in situ in OLP compared to normal oral mucosa, and seems to be related to the epithelial thickness.     

T细胞免疫和细胞凋亡在口腔扁平苔藓发病中的作用

目的通过探讨口腔扁平苔藓（OLP）中细胞凋亡情况及CD4＋、CD8＋T细胞和CD4/CD8比例的变化分析细胞免疫与细胞凋亡的关系,进一步了解OLP的发病机制。方法应用免疫组化SP法检测27例OLP组织中CD4＋、CD8＋T细胞的表达水平,并用原位末端转移酶标记法（TUNEL）定位检测17例OLP中细胞凋亡情况。结果OLP组固有层中CD4＋、CD8＋T细胞明显高于对照组（P＜0.05）,CD4/CD8值降低。OLP组中上皮内细胞凋亡指数高于对照组,固有层淋巴细胞凋亡指数明显低于对照组。结论OLP组固有层中CD4＋、CD8＋T细胞浸润的增加、CD4/CD8比值的变化及OLP中上皮细胞和固有层淋巴细胞凋亡异常,说明细胞免疫功能紊乱和细胞凋亡异常在OLP发病中起重要作用。     

Intra-epithelial subpopulations of T lymphocytes and Langerhans cells in oral lichen planus

This study has addressed the question of whether there is selective recruitment and distribution of intra-epithelial leucocytes in lesions of oral lichen planus (OLP). T-lymphocyte subsets were examined in the epithelium and peripheral blood of patients and controls using flow cytometry and double immunofluorescence, and the relationship between keratinocyte intercellular adhesion molecule-1 (ICAM-1) expression with T-lymphocyte and Langerhans cell (LC) distribution was examined. The circulating 'memory'subset (CD45RO⁺) of T-helper cells (CD4⁺) was increased from 49.1% in controls to 65.7% in patients ( P = 0.005), while the 'naive'subset (CD45RA⁺), which was absent from control epithelium, comprised 24% of helper cells in OLP ( P =0.037) and all T-cell and LC counts were significantly raised in ICAM-1-expressing areas of epithelium. These data demonstrate changes in intra-epithelial T-lymphocyte and LC populations compared with normal oral mucosa and suggest there is selective recruitment in OLP. In addition, Keratinocyte ICAM-1 expression does appear to be associated with accumulation of infiltrating T lymphocytes and LC.     

调节性T细胞和Th17细胞在OLP中的表达

目的：通过观察调节性T细胞（regulatory Tcells,Treg）和Thl7细胞（helper Tcells17,Th17）在口腔扁平苔藓（OLP）组织中的表达情况,探讨其在OLP发生发展过程中的变化。方法：应用免疫组织化学双标记技术检测35例OLP患者和19例对照组口腔黏膜组织中CD25＋Foxp3＋、CD4＋IL-17＋细胞的表达。结果：OLP组病损组织中有大量CD25＋Foxp3＋细胞浸润,较对照组显著增多,两者差异非常显著（P〈0．01）。CD4＋IL-17＋细胞在OLP组织中的表达较正常口腔黏膜组织有增加趋势,但差异无统计学意义（P〉0．05）。经进一步统计学分析,CD25＋Foxp3＋细胞和CD4＋IL-17＋细胞数量改变在OLP组织中表达呈正相关（P〈0．05）。结论：Treg细胞的数量在OLP组织中增多,Thl7细胞可能协同Treg细胞,在OLP发生发展过程中发挥了一定的作用。     

Expression of TGF-beta receptors in CD8+ T cells of oral lichen planus

OBJECTIVE: To investigate the expression of TGF-beta receptors in CD8+ T cells of oral lichen planus (OLP). METHODS: Immunohistochemical double labeling technique was used to examine the expression of TGF-betaR I and TGF-betaR II in CD8+ T cells of 28 OLP patients and in 10 controls. The results were compared between the two groups. RESULTS: The double labeled cells were negative in controls. The positive rates of double labeled cells of CD8+/TGF-betaR I and CD8+/TGF-betaR II in OLP were (8.82 +/- 9.98)% and (1.11 +/- 2.94)% respectively. CONCLUSIONS: The expression level of TGF-betaR II in CD8+ T cells of OLP did not increase compared with the controls, but the expression of TGF-betaR I increased. The results indicate the abnormal TGF-beta signal transduction in CD8+ T cells of OLP, which may contribute to the persistence of the chronic inflammation in OLP.     

Intra-epithelial CD8+ T cells and basement membrane disruption in oral lichen planus.

BACKGROUND: We investigated basement membrane (BM) disruption and the distribution of mast cells (MCs) and T cell subsets, in oral lichen planus (OLP) and normal buccal mucosa (NBM) using immunohistochemistry. In OLP, there were increased numbers of tryptase+ MCs in areas of BM disruption (P < 0.05). METHOD: We identified clusters of intraepithelial CD8+ T cells in OLP, specifically in regions of BM disruption. The number of intraepithelial CD8+ T cells in regions of BM disruption was significantly greater than in regions of BM continuity (P < 0.05). RESULTS: There were comparable numbers of lamina propria CD8+ T cells in regions of BM disruption and BM continuity. The number of CD4+ T cells in the epithelium and lamina propria of OLP lesions did not vary between regions of BM disruption and BM continuity. CONCLUSION: These data suggest a role for MCs in epithelial BM disruption in OLP. CD8+ T cells may migrate through BM breaks to enter the OLP epithelium.     

T cell antigen receptor expression by intra-epithelial lymphocytes in oral lichen planus

The distribution of T lymphocytes expressing the αβ or γδ heterodimer of the T cell receptor (TCR) was examined in normal oral mucosa (NOM) and reticular oral lichen planus (OLP) using a panel of antibodies specific for CD3, the αβ TCR and the γδ TCR. Intra-epithelial lymphocytes were counted and epithelial surface length was measured by image analysis. T cells in the lamina propria were not quantified. Total intra-epithelial lymphocytes were increased in OLP compared with NOM (p=0.0004). The proportions of cells expressing the γδ TCR in NOM and OLP were 10% and 9.3%, respectively, suggesting there is no selective recruitment from the circulation of either αβ or γδ TCR-bearing cells into normal oral epithelium or that affected by OLP The role. if any, of γδ T cells in the pathogenesis of OLP remains to be determined.     

Immunohistopathological study of the oral lichenoid lesions of chronic GVHD

BACKGROUND: Chronic graft-vs.-host disease (cGVHD) is a common and serious complication after bone marrow transplantation (BMT). However, the detailed process of oral lichenoid lesions of cGVHD is still unknown. Therefore, we investigated the immunohistopathological features of cGVHD compared with oral lichen planus (OLP) and healthy controls. METHODS: Nineteen allogenic BMT recipients with a histopathological diagnosis of cGVHD were investigated. We investigated the immunohistopathological features of cGVHD compared with OLP and healthy controls. RESULTS: Immunohistopathological features showed that the infiltrations of CD4-positive T cells of cGVHD and OLP were significantly larger than those of the normal oral mucosa (P < 0.005). A larger number of CD8-positive T cells was infiltrated in cGVHD and OLP compared with the normal oral mucosa (P < 0.001). The difference in the number of CD4- and CD8-positive T cells between cGVHD and OLP was not significant. The infiltrations of Langerhans cells (CD1a) in cGVHD and OLP were significantly larger than those in the normal oral mucosa (P < 0.005). The difference in the number of Langerhans cells between cGVHD and OLP was not significant. CD68-positive macrophages were more frequently seen in cGVHD and OLP than in the normal oral mucosa (P < 0.0001). The difference in the number of CD68-positive macrophages between cGVHD and OLP was not significant. CONCLUSIONS: It is suggested that Langerhans cells and CD8-positive T cell may play a major role in the pathogenesis of the oral lichenoid lesions of cGVHD, and the immune response was inducted in OLP as well as the oral lichenoid lesion of cGVHD in this study.