Immunohistochemical demonstration of T cell subsets and accessory cells in oral lichen planus

The nature and distribution of mononuclear cells in 30 non-ulcerated lesions of oral lichen planus (OLP) was investigated, using an immunoperoxidase technique. Most of the infiltrating cells consisted of a mixture of Leu 2a+ and Leu 3a+/3b+ T cells present in the stroma. This study proved histometrically that the emigration of lymphocytes through subepithelial vessels was not selective for major subsets of T cells and subsequent migration to the epithelium was predominant in suppressor/cytotoxic T cell infiltration. HLA-DR+/DQ+ monocyte/macrophage and Langerhans cells formed a relatively minor component of the cellular infiltrates, whereas a considerable number of T cells expressed the MHC antigens. Also, the keratinocytes of the epithelium expressed only DR antigens. These results support the concept that LP is associated with lymphokine-generated inflammation induced by helper/inducer T cells or activated T cells which would include direct basal cell damage or local immunosuppression by suppressor/cytotoxic T cells. Furthermore, this study suggests that monocytes/macrophages and Langerhans cells played a role in antigen presentation, and also that keratinocytes may possess a similar function.     

Immunohistochemical demonstration of T cell subsets and accessory cells in oral lichen planus

The nature and distribution of mononuclear cells in 30 non-ulcerated lesions of oral lichen planus (OLP) was investigated, using an immunoperoxidase technique. Most of the infiltrating cells consisted of a mixture of Leu 2a+ and Leu 3a+/3b+ T cells present in the stroma. This study proved histometrically that the emigration of lymphocytes through subepithelial vessels was not selective for major subsets of T cells and subsequent migration to the epithelium was predominant in suppressor/cytotoxic T cell infiltration. HLA-DR+/DQ+ monocyte/macrophage and Langerhans cells formed a relatively minor component of the cellular infiltrates, whereas a considerable number of T cells expressed the MHC antigens. Also, the keratinocytes of the epithelium expressed only DR antigens. These results support the concept that LP is associated with lymphokine-generated inflammation induced by helper/inducer T cells or activated T cells which would include direct basal cell damage or local immunosuppression by suppressor/cytotoxic T cells. Furthermore, this study suggests that monocytes/macrophages and Langerhans cells played a role in antigen presentation, and also that keratinocytes may possess a similar function.     

Immunohistochemical study of oral lesions of lichen planus: diagnostic and pathophysiologic aspects

The immunophenotype of lymphoid cells in the epithelium and lamina propria of the oral mucosa were examined in patients with lichen planus, nondysplastic leukoplakia, leukoplakia with lichen planus, and other unrelated lesions. In all groups T lymphocytes were predominant; however, the T4/T8 lymphocyte ratio was higher with lichen planus than with other groups. This may be of diagnostic value in the histologic evaluation of oral lesions not typical of lichen planus. Finally, a higher percentage of Langerhans cells were observed in lichen planus. An immunologic pathogenesis of lichen planus is proposed.     

Valuation of exfoliative cytology as prediction factor in oral mucosa lesions

The aim of this study was immunolabeling oncoproteins Ck14, p53, p21 and Bcl-2 in order to evaluate their expression in premalignant and malignant stomatological lesions in oral epithelial, and to compare this expression with exfoliative cytology alterations in the same patients. It was studied biopsies and cytologies of 13 subjects with oral lichen planus, with or without Human Papilloma Virus (HPV), leukoplakia and squamous cell carcinoma clinically diagnosed and confirmed by anatomopathological studies. The oral lichen planus lesion presented binuclei orange cells; and in leukoplakia lesions only orange stained was observed; meanwhile koilocytes, inflammatory cells, enlarge nuclear volume and pathogenic microorganisms were observed in the HPV infections and squamous cells carcinoma (SCC). The Ck14, p53, p21 and Bcl-2 proteins were found modified in the leukoplakia, oral lichen planus and cancer. Cytological alterations and positive immunolabeling or over-expression of Ck14 cytokeratine in the upper epithelial stratus should be indicator of malignant transformations as doing subsequence exams.     

A comparative immunological analysis of the oral mucosa in chronic graft-versus-host disease and oral lichen planus.

Oral mucosal biopsies of 12 allogeneic marrow transplant recipients with chronic graft-versus-host disease (GVHD) involving the mouth were compared with biopsies taken before transplantation. They were also compared with biopsies from otherwise healthy patients with oral lichen planus, and with those from a control group of normal individuals. Biopsies from chronic GVHD exhibited a low number of infiltrating T lymphocytes (CD3 cells) compared with those from oral lichen planus, which showed intense cell infiltration (p less than 0.005). The ratio of CD4 to CD8 cells in biopsies taken after the manifestation of chronic GVHD exhibited no consistent variation compared with those taken before transplantation or with biopsies of oral lichen planus. The CD4/CD8 ratio in all groups investigated varied between 4:1 and 6:1. The number of natural killer cells (CD57), was increased in biopsy specimens taken before transplantation compared with the other groups. The frequency of homing receptor, Leu-8 bearing T cells was low in the biopsy specimens of all groups, compared with the corresponding frequency in peripheral blood (10-45 and 60-90%, respectively; p less than 0.001). In the biopsies from chronic GVHD and oral lichen planus the number of lymphocytes with transferrin receptors was increased compared with the pretransplant and control groups. Virtually no infiltrating cells were carrying interleukin-2 receptors (CD25) in any of the groups studied. Langerhans cells (CD1) were more frequently found in the specimens from chronic GVHD and oral lichen planus than in the pretransplant specimens and the control group (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

In situ lymphocyte subpopulations from active versus stable periodontal sites

The purpose of this study was to evaluate lymphocyte subset densities and distributions within gingival biopsies from active sites (greater than or equal to 2 mm clinical attachment loss within three months of biopsy) versus clinically similar but stable or healthy sites. Small interproximal gingival biopsies representing at least one of each of the above categories were obtained from each of 20 periodontal maintenance patients. Serial cryostat sections displaying a cross section of the gingiva were labeled with monoclonal antibodies for (1) pan T cells, (2) T cytotoxic/suppressor cells, (3) T helper/inducer cells and (4) pan B cells and were developed using an avidin-biotin-peroxidase system. Lymphocyte populations were enumerated in repeatable fields from the sulcular, middle and oral one-third of each section. Relative proportions of the same lymphocyte subsets were analyzed in peripheral blood samples from the same patients using direct immunofluorescence. Pan B cells were significantly more prevalent in infiltrates from active sites than in stable (P less than 0.05) or healthy (P less than 0.01) sites. The T/B cell ratio was also significantly lower in active than stable biopsies (P less than 0.05), and in active biopsies versus blood (P less than 0.05). The T helper/T suppressor cell ratio did not vary significantly between blood and any gingival tissue disease group or location, but a trend toward lower relative numbers of T helper cells in the sulcular infiltrates of active sites was noted. These results support the premise that active periodontal sites display elevated B cell populations and abnormal immune regulation possibly involving the T helper cell subset.     

口腔扁平苔藓T细胞受体BV基因的优势取用初探

目的:研究口腔扁平苔藓(oral lichen planus,OLP)患者损害组织中浸润的T细胞受体(T cell receptor,TCR)BV基因的取用格局。方法:采用实时定量聚合酶链反应,分析OLP患者损害组织中浸润的T细胞和外周血中T细胞TCR BV基因的取用格局。采用GraphPad Prism version 5.00软件对数据进行Mann-Whitney U检验。结果:43例OLP患者的损害组织对BV4、BV14和BV18基因的取用显著高于39例OLP患者外周血对这些BV基因的取用。结论:OLP患者损害组织浸润的T细胞优势取用BV4、BV14和BV18基因,提示带有BV4、BV14和BV18基因的T细胞参与了OLP的发病。     

Induction and upregulation of adhesion receptors in oral and dermal lichen planus

The expression pattern of well-defined cell surface adhesion receptors called VLA-family, LFA-1 and ICAM-1 was determined semiquantitatively in biopsies of oral (n = 12) and dermal lichen planus (n = 5) and compared to normal uninvolved human oral mucosa (n = 12) and skin (n = 12) using an indirect immunoperoxidase technique. In both oral and dermal lichen planus, an induction of the beta 1-integrins VLA-1 and VLA-3 and an upregulation of VLA-6 was found in T cells infiltrating the basement membrane zone. These cell surface molecules function as receptors for collagen, fibronectin and laminin. A focal induction of ICAM-1 on basal keratinocytes could be detected at sites of intramucosal T cells. These results suggest that investigated adhesion receptors are crucially involved in the aggregation of T cells in both conditions. Further investigations have to be done to determine the functional role of these adhesion receptors in lichen planus.     

The frequency of Candida in oral lichen planus

ABSTRACT – Histologic material of typical lichen planus lesions from 43 patients was studied. Two sections of each specimen were stained with hematoxylin-eosin and 10 sections by the PAS method. Only 1 of 43 biopsies was invaded by Candida, and hyphae were present in all of the 10 PAS-stained sections of this case. The results show that oral lichen planus has a considerably lesser susceptibility than oral leukoplakia to invasion by Candida albicans.     

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目的研究鸟氨酸脱羧酶（ODC）与口腔白斑的发生、发展乃至癌变潜能的关系。方法选取2009—2010年大连医科大学附属第一医院口腔科收治且经病理确诊的口腔白斑患者22例,以其病变黏膜组织为研究对象,同时以11例正常口腔黏膜、22例口腔扁平苔藓组织和22例口腔鳞癌组织为对照。采用免疫组化法检测ODC在各种组织中的表达,并对阳性率进行比较分析。结果在口腔正常黏膜、扁平苔藓、白斑和鳞癌组织中ODC的阳性率依次增加;ODC在口腔扁平苔藓中的阳性率高于正常黏膜,但差异无统计学意义（P〉0.05）,ODC在口腔白斑中的阳性率与正常黏膜和扁平苔藓的差异均有统计学意义（P〈0.05）,口腔鳞癌组织中ODC的阳性率显著高于其余组（P〈0.05）。结论 ODC表达程度可用于判断口腔白斑的恶变倾向及口腔鳞癌的恶性程度。     

Activation marker analysis of mononuclear cell infiltrates of oral lichen planus in situ

Abstract – Monoclonal activation markers (la, Tac, T9, and 4F2) were used to detect the degree of activation of mononuclear cells in the inflammatory infiltrates of oral lichen planus in situ. In addition the specimens were stained with the following monoclonal antibodies: T4, T8, T11, Ml, and pan-B. T-lymphocyte was the predominant cell type in the inflammatory infiltrates. According to the results of the activation marker analysis, the majority of the Tlymphocytes were resting. However, activated cytotoxic T8 and 4F2 T-cells were located close to damaged basal cells; this finding may suggest that they are responsible for the damage and supports the claim that a cell-mediated immune response participates actively in local pathogenetic mechanisms in oral lichen planus.     

Activation marker analysis of mononuclear cell infiltrates of oral lichen planus in situ

Monoclonal activation markers (Ia, Tac, T9, and 4F2) were used to detect the degree of activation of mononuclear cells in the inflammatory infiltrates of oral lichen planus in situ. In addition the specimens were stained with the following monoclonal antibodies: T4, T8, T11, M1, and pan-B. T-lymphocyte was the predominant cell type in the inflammatory infiltrates. According to the results of the activation marker analysis, the majority of the T-lymphocytes were resting. However, activated cytotoxic T8 and 4F2 T-cells were located close to damaged basal cells; this finding may suggest that they are responsible for the damage and supports the claim that a cell-mediated immune response participates actively in local pathogenetic mechanisms in oral lichen planus.     

Occurrence of oral leukoplakia and lichen planus in diabetes mellitus

The occurrence of oral leukoplakia and lichen planus in 1600 patients with diabetes mellitus (815 type 1: insulin-dependent, 761 type 2: non-insulin-dependent)-under care at the International Medicine Department-was studied. Precancerous lesions and conditions were diagnosed and grouped according to internationally accepted criteria. The prevalence of oral leukoplakia in diabetic patients was 6.2%, as compared to 2.2% in the healthy controls, that of oral lichen was 1.0% in the test-, and 0.0% in the control group. Leukoplakia and lichen both showed the highest occurrence in the second year of established diabetes, and their prevalence was higher among insulin-treated diabetics. Smokers were more often affected, by both kind of lesions, oral lichen showed a more frequent association with candidiasis. The prevalence of oral leukoplakia and lichen in diabetes mellitus patients was higher, than average ratios in population samples from the same country.     

白细胞相关免疫球蛋白样受体-2和转化生长因子-β在口腔扁平苔藓患者外周血表达及意义

目的:探讨白细胞相关免疫球蛋白样受体-2(LAIR-2)和转化生长因子-β(TGF-β)在口腔扁平苔藓患者外周血表达及意义。方法:选取53例口腔扁平苔藓患者和50例健康者,利用流式细胞仪检测外周血Treg细胞上LAIR-2表达,利用ELISA法对血清中TGF-β水平进行检测。结果:LAIR-2在口腔扁平苔藓患者外周血Treg细胞上阳性表达率为(4.62±0.33)%,显著低于对照组的(6.47±0.28)%,差异有统计学意义(P<0.05);口腔扁平苔藓患者外周血中TGF-β水平显著高于对照组,差异有统计学意义(P<0.05);Pearson相关分析显示,口腔扁平苔藓患者外周血Treg细胞上LAIR-2阳性表达和TGF-β水平呈负相关(r=-0.416,P=0.011)。结论:LAIR-2在口腔扁平苔藓患者外周血Treg细胞中呈低表达,而外周血TGF-β水平升高,二者可能共同参与了T细胞介导免疫抑制作用,与口腔扁平苔藓发生及进展有关。     

Expression of integrin α9 subunit and tenascin in oral leukoplakia, lichen planus, and squamous cell carcinoma

OBJECTIVES: Integrin alpha9 subunit is a member of beta1 integrin family and binds tenascin (TN). It is expressed by stratified squamous epithelium and may be associated with cell differentiation and growth. We studied if the expression of alpha9 integrin and TN is altered in leukoplakia, lichen planus, and squamous cell carcinoma (SCC).METHODS: Frozen sections of tissue samples obtained from normal human keratinized (16 subjects) and non-keratinized (three subjects) oral mucosa, oral leukopakias with dysplasia (19 subjects), reticular type lichen planus (nine subjects), or oral mucosal SCC (23 subjects) were stained immunohistochemically with antibodies against alpha9 integrin and TN.RESULTS: In contrast to its most prominent localization at the cell membranes of the basal epithelial cells in the normal mucosa, alpha9 integrin was localized in a more diffuse pattern with focal loss of expression at the epithelial cell membranes in leukoplakic dysplasia, lichen planus, and SCC. In some areas of SCC, alpha9 integrin localized throughout all cell layers of the tumor epithelium. In most areas, alpha9 integrin colocalized with TN but in heavily inflamed areas there was focal loss of TN and alpha9 integrin at the basement membrane zone. CONCLUSIONS: The findings show that alpha9 integrin expression is altered in leukoplakic dysplasia, lichen planus, and SCC.     

Clinical and histologic studies on electrogalvanically induced oral white lesions.

Among 1,128 patients with oral leukoplakia and 326 patients with oral lichen planus included in long-term follow-up studies, thirty-two patients showed lesions of the oral mucosa which could be attributed to electrogalvanism. The material consisted of twenty female and twelve male patients. The clinical diagnosis was leukoplakia in sixteen patients and oral lichen planus in the remaining sixteen patients. Histopathologic characteristics were analyzed and correlated to the clinical findings. In five cases malignant transformation developed. The term electrogalvanic white lesions is suggested as a common denominator for these mucosal changes, which seem to take the shape of lichen planus as often as that of leukoplakia.     

Incidence rates for oral leukoplakia and lichen planus in a Japanese population

BACKGROUND: Data on the incidence rates of potentially malignant diseases of the oral cavity in different populations is meagre. This is the first study to report on the age-specific incidence of oral leukoplakia and oral lichen planus from an industrialized country. METHODS: Annual screening for oral cancer and pre-cancer was undertaken in Municipal Health Centres in Tokoname city, Japan from 1995 to 1998. A total of 9536 volunteers aged 40-95 years participated in this programme. A cohort of 6340 (67%) subjects attended annual mouth examinations following a negative screen result at entry, allowing 13 072 person-years of observations. Some associated risk factors (tobacco and alcohol misuse) and health-related variables were also evaluated. RESULTS: Over a 4-year follow-up period, 18 new oral leukoplakias (all homogenous; 11 idiopathic and seven tobacco-associated) and 24 oral lichen planus (22 reticular, one erythematous and one ulcerative) were detected at screening and confirmed by re-examination at specialist units. The age-adjusted incidence rate for leukoplakia was 409.2 (95% CI: 90.6-727.9) in male and 70.0 (95% CI: 17.9-121.8) in female per 100,000 person-years observations. For lichen planus, the corresponding rates were 59.7 (95% CI: 7.4-112.1) and 188.0 (95% CI: 96.0-280.1). The age-adjusted incidence rate for tobacco-associated leukoplakia in males was almost 12 times compared with female (560.3 vs. 45.2 per 100,000). Age-specific incidence rates for oral leukoplakia varied by age groups. New oral leukoplakias were more prevalent on gingival/alveolar ridge (33.3%) than in other oral sites, and lichen planus at buccal site (33.3%). Prevalence of smoking habits among those positive for leukoplakia (38.9%) was higher compared with the screen-negatives (26.4%) but these differences did not reach statistical significance (P = 0.232). Regular drinking was not related to occurrence of either oral leukoplakia or oral lichen planus. In cases with diabetes mellitus, relative risk for oral lichen planus adjusted by logistic regression was 6.4 (95% CI: 2.4-17.6), suggesting an association. CONCLUSIONS: The reported incidence rates for oral leukoplakia in this Japanese population are somewhat higher to those reported from India, the risk habits of the two groups being markedly different. The reported rates for oral leukoplakia and lichen planus allow estimation of service needs in specialist oral medicine clinics and for the training of primary care dentists. A high incidence of idiopathic leukoplakia found in this study raises challenges to the strategy of screening high-risk populations aimed at conserving resources.     

MMP-28在复发性阿弗他溃疡、口腔扁平苔藓、口腔白斑中的表达和意义的研究

目的　探讨MMP-28在复发性阿弗他溃疡、口腔扁平苔藓、口腔白斑中的表达和意义。方法　分别采用免疫组化和Western-blot方法检测MMP-28在14例复发性阿弗他溃疡、16例口腔扁平苔藓、15例口腔白斑病中的表达,并与12例正常口腔黏膜进行比较。结果　口腔扁平苔藓、口腔白斑组织中MMP-28的表达高于正常口腔黏膜和复发性阿弗他溃疡组织,白斑组织中表达高于扁平苔藓组织。结论　MMP-28在口腔扁平苔藓、白斑患者中有表达,且在白斑患者中高表达,提示其可能参与了癌变的发病过程。     

Immunohistochemical analysis of cells in mucosal lesions of oral lichen planus

We immunohistochemically analyzed the immunological background of the pathogenesis of oral lichen planus (OLP). Abundant lymphocytes infiltrated OLP mucosal lesions, particularly in satellite cell necrosis (SCN) regions, and cytotoxic/suppressor T lymphocytes were predominant in seven of 10 OLP cases. Some carried IL-2 receptors, particularly in SCN. Keratinocytes of the mucosal lesions expressed both HLA-ABC and HLA-DR antigens. This suggests that activated cytotoxic/suppressor T lymphocytes may play a major role in cytotoxity to keratinocytes as effector cells in OLP. OKM1-, OKM5+, HLA-DR+ and IL-1+ cells, vascular endothelial cells and clusters of spindle-shaped or oval cells, which had the same surface characteristics as a monocyte macrophage subset, were abundant and, together with migrating lymphocytes, might play a role in the immune response in mucosal lesions of OLP.     

口腔扁平苔藓病损中肥大细胞形态及分布特点研究

目的:研究肥大细胞亚型在口腔扁平苔藓中的特征,探讨肥大细胞与扁平苔藓发病的关系。方法:应用阿辛蓝)萨红染色法显示口腔扁平苔藓组织中肥大细胞,计算成熟型和非成熟型肥大细胞的构成比;应用LUZEX-F图像分析系统检测两型肥大细胞的面积,并观察形态特点。结果:口腔扁平苔藓病损组织中非成熟型和成熟型肥大细胞构成比与正常组织间有显著性差异(P<0101);口腔扁平苔藓的丘疹型、网纹型和糜烂型间非成熟型和成熟型肥大细胞构成比有差异(P<0105);非成熟型和成熟型肥大细胞面积有显著性差异(P<0101),其胞浆内颗粒的大小、数量及分布区域均不同。结论:肥大细胞可能参与了口腔扁平苔藓的病理损害过程。