The activation of Langerhans cells in oral lichen planus

The numbers of CD1, HLADR, HLADP and HLADQ positive, intraepithelial, dendritic cells were compared in lesions of oral lichen planus and normal oral mucosa using an immunoalkaline phosphatase technique. In normal mucosa, there were equal numbers of CD1 and HLADR positive cells but significantly fewer cells were positive for HLADP (P less than 0.001) and HLADQ (P less than 0.05). In lichen planus, the cells appeared more dendritic and equal numbers of CD1, HLADR, HLADP and HLADQ positive cells were found, with significantly more HLADP (P less than 0.01) and HLADQ (P less than 0.05) positive cells than in normal mucosa. There was no change in the number of CD1 and HLADR positive cells. These results show that although there is no change in the total number of Langerhans cells (CD1 positive cells) in lichen planus, there is an increase in Class II major histocompatibility antigen expression. This suggests that in lichen planus, Langerhans cells are immunologically active and play a role in lesion development.     

Expression of MHC Class II antigens (HLA DR, DP and DQ) by keratinocytes in oral lichen planus

The incidence and distribution of keratinocytes expressing the major histocompatability complex antigens HLA DR, DP and DQ and their relationship to the density of the inflammatory infiltrate was determined in lesions of oral lichen planus and normal mucosa using an immunoalkaline phosphatase technique. Seven of eight biopsies of lichen planus showed evidence of keratinocyte HLA DR expression but the pattern was variable both within and between biopsies. A significant increase in density of lymphocytes was found beneath those areas showing HLA DR expression throughout the prickle cell layer compared with those areas showing patchy or no expression. No evidence for keratinocyte expression of HLA DP or DQ was found. These results suggest that expression of HLA DR by keratinocytes in lichen planus may be induced by the lymphocytic infiltrate perhaps as a result of interferon gamma production. The functional significance of such MHC Class II expression remains unknown.     

Expression of CD1 and HLA-DR by Langerhans cells (LC) in oral lichenoid drug eruptions (IDE) and idiopathic oral lichen planus (LP)

Numbers of Langerhans ceils (LC) expressing the common thymocyte antigen (T6/CD1) are similar in oral lichen planus (LP) and in normal oral epithelium: however, expression of class II major histocompatibility antigens (HLA-DR/Ia) by Langerhans cells is greater in lichen planus than in normal epithelium, a phenomenon believed to be associated with activation and antigen presentation. This study quantified the numbers of T6+ve and HLA-DR + ve Langerhans cells in oral lichen planus and lichenoid drug eruptions (LDE) to investigate whether differences may reflect differing routes of antigen presentation. Six patients with oral lichenoid drug eruptions and six control idiopathic oral lichen planus patients had lesional biopsies. An immunoperoxidase technique was used to demonstrate binding of T6 and HLA-DR antibodies to identify dendritic intra-epithelia! cells as Langerhans cells and activated Langerhans cells, respectively. In lichenoid drug eruptions, the number of HLA-DR+ve LC was significantly lower than the number of T6+ve LC ( P < 0.05), whereas in idiopathic lichen planus the numbers of T6+ve and HLA-DR+ve LC did not differ significantly ( P = 0.20). The results provide evidence for differences in the routes of antigen presentation in lichenoid drug eruptions and idiopathic lichen planus.     

Identification of the AgNORs, PCNA and ck16 proteins in oral lichen planus lesions

The expression of proliferating cell nuclear antigen (PCNA), cytokeratin 16 (ck16) and Ag nucleolar organizer regions (AgNORs) were assessed in 20 cases of lichen planus, 20 cases of keratosis and 20 cases of normal oral mucosa in order to evaluate the rate of keratinocyte proliferation in these tissues. Three hundred cells were counted in each sample: 100 basal cells, 100 suprabasal cells and 100 squamous cells. The mean number of AgNORs and the percentage of PCNA positive cells were calculated. Except from similar staining of suprabasal cells of lichen planus and keratosis, PCNA and AgNORs values were higher in all layers of lichen planus than in both keratosis and normal oral mucosa. The three groups showed similar ck16 immunostaining: all of the cells were positive, except those of the basal layer. The results suggest that the keratinocyte proliferation index is higher in lichen planus than in keratosis and normal mucosa. Besides, ck16 should not be used to differentiate the entities studied.     

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.     

The expression of HLA-DR on keratinocytes in oral lichen planus

HLA-DR is a Class II histocompatibility antigen which has recently been reported to occur in increased amounts in dermal and oral lichen planus. Its expression in epithelium was previously thought to be limited to Langerhans cells. In this study, formalin-fixed sections of oral lichen planus and a variety of other oral mucosal lesions were stained with a monoclonal antibody to HLA-DR using an indirect immunofluorescence test. The expression of HLA-DR by keratinocytes did not appear to be a specific marker for lichen planus as demonstrated by the reactivity of the epithelium in a variety of lesions of the oral mucosa. If HLA-DR expression is considered to be an inducible function, perhaps in response to gamma interferon secreted by activated lymphocytes, then keratinocyte reactivity would not be expected to occur only in lichen planus.     

The expression of HLA-DR on keratinocytes in oral lichen planus

HLA-DR is a Class FI histocompatibility antigen which has recently been reported to occur in increased amounts in dermal and oral lichen planus. Its expression in epithelium was previously thought to be limited to Langerhans cells. In this study, formalin-fixed sections of oral lichen planus and a variety of other oral mucosal lesions were stained with a monoclonal antibody to HLA-DR using an indirect immunofluorescence test. The expression of HLA-DR by keratinocytes did not appear to be a specific marker for lichen planus as demonstrated by the reactivity of the epithelium in a variety of lesions of the oral mucosa. II HLA-DR expression is considered to be an inducible function, perhaps in response to γ interferon secreted by activated lymphocytes, then keratinocyte reactivity would not be expected to occur only in lichen planus.     

CD133在口腔扁平苔藓和口腔鳞状细胞癌中的表达及其临床意义

目的探究肿瘤干细胞标记物CD133在口腔正常黏膜、口腔扁平苔藓（OLP）及口腔鳞状细胞癌（OSCC）中的表达情况及临床意义,评估其作为OLP恶性转化的早期诊断指标、OSCC治疗干预靶标的临床价值,为进一步研究口腔黏膜癌变机制提供基础。 方法回顾性分析10例正常口腔黏膜、60例OLP、60例OSCC患者的临床资料,运用免疫组织化学技术检测各组病理组织中CD133表达情况,采用Mann-Whiney秩和检验比较各组间CD133表达差异,卡方检验统计分析CD133与各临床因素的关系。采用免疫组织化学技术和免疫印迹技术检测人口腔癌前病变细胞株（DOK）和人OSCC细胞株（CAL-27）中CD133的表达情况,t检验比较CD133在DOK与CAL-27细胞株中含量差异。 结果口腔正常黏膜、OLP、OSCC三组中,CD133的阳性率为0（0/10）、31.67%（19/60）、63.33%（38/60）,表达逐渐增强。CD133在口腔正常黏膜与OLP表达强度差异有统计学意义（Z=-2.046,P= 0.041）。CD133在OLP与OSCC表达强度差异具有统计学意义（Z=-3.777,P<0.001）。CD133在DOK中弱阳性表达,在CAL-27中阳性表达,DOK与CAL-27中CD133含量差异有统计学意义（t=-5.029,P= 0.001）CD133与OSCC的临床分期和淋巴结转移有关。 结论CD133作为评估OLP恶性转化潜能的指标及OSCC早期治疗干预靶标可能具有重要临床价值。     

Langerhans cells expressing HLA-DQ, HLA-DR and T6 antigens in normal oral mucosa and lichen planus

We compared Langerhans cells (LC) expressing HLA-DQ, HLA-DR and T6 antigens in biopsies from the same oral mucosal site in 12 patients with oral lichen planus and eight healthy volunteers. LC expressing each antigen were observed in all the specimens, but in lichen planus the cells were located in higher levels of the epithelium than in controls. Compared with controls, lichen planus contained significantly more HLA-DQ-positive LC (P = 0.04) and fewer HLA-DR-positive LC (P = 0.05), but there was no such difference in T6-positive LC. In lichen planus specimens, there were significantly more LC expressing HLA-DQ and T6 than HLA-DR (P = 0.0001 and 0.02 respectively); no such differences were found in normal mucosa. Epithelial cells in lichen planus expressed HLA-DR antigen, but not HLA-DQ or T6 antigens. We conclude that in lichen planus there is modulation of HLA-DR and HLA-DQ antigen expression by LC, or differences in the number of LC expressing those antigens.     

Expression of CDw29 and CD45R antigens on epithelial cells in oral lichen planus

The CD45R and CDw29 antigens are expressed on naive and primed helper T cell populations which serve suppressor-inducer or helper-inducer functions, respectively. These antigens may also be expressed on epithelial cell subpopulations. In the present study, monoclonal antibodies reacting with T lymphocytes and Langerhans cells (LC) were used to characterize the expression of CD45R and CDw29 antigens in oral lichen planus. CDw29 was expressed by LC and lymphocytic cells whereas keratinocyte reactivity varied from negative through to full thickness staining. Expression of CD45R was confined to intraepithelial cells with either lymphocytic or dendritic morphology. A relatively constant ratio of CD1a + LC to CD45R + cells (2:1) was seen. These results demonstrate the existence of intraepithelial cells expressing antigens which are functionally important in T cell responses and which may provide local immunoregulatory influences.     

CD44在口腔扁平苔藓中的表达及意义

目的 探讨口腔扁平苔藓病变中粘附分子CD44H、CD44V3表达的意义。方法 应用免疫组织化学SP法对62例口腔扁平苔藓，其中糜烂型扁平苔藓14例，非糜烂型扁平苔藓48例，21例慢性盘状红斑狼疮，10例正常粘膜CD44H、CD44V3的表达进行观察。结果 扁平苔藓病损区组织的染色以基底细胞、棘层细胞下调明显。结论 CD44参与口腔扁平苔藓的发病过程。     

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.     

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.     

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.     

Langerin-expressing and CD83-expressing cells in oral lichen planus lesions

OBJECTIVE: Dendritic Langerhans cells (LCs) have been attributed a role in the pathogenesis of lichen planus as autoantigen-presenting cells initiating expansion of autoreactive T cells. Langerin and CD83, which are cell molecules expressed on LCs, are associated with antigen presentation. The present study examined expression of Langerin and CD83 molecules on LCs in patients with oral lichen planus (OLP). MATERIAL AND METHODS: Biopsies were obtained from seven patients with OLP. Oral mucosa from seven healthy subjects served as controls. Monoclonal antibodies (mAbs) were used in standard immunohistochemical procedures to visualize CD1a-, Langerin-, and CD83-molecule-expressing cells. RESULTS: CD1a+ and Langerin+ cells were found in significantly higher frequencies in OLP epithelium compared with healthy oral epithelium (p<0.01 and p<0.05, respectively); however, the frequency of CD83+ cells did not differ (p>0.05). The connective tissue in OLP lesions showed significantly higher frequencies of CD1a+, Langerin+, and CD83+ cells compared with healthy connective tissue (p<0.01, p<0.01, and p<0.05). CD1a+ and Langerin+ cells in OLP and healthy epithelium had a dendritic morphology. CONCLUSIONS: The study shows increased numbers of CD1a- and Langerin-expressing LCs in OLP compared with healthy controls. In the connective tissue, CD83+ cells with dendritic morphology were localized to regions of lymphocyte clusters. The presence of CD83+ dendritic cells in areas of lymphocyte clusters in the connective tissue of OLP lesions indicates the possibility of ongoing autoantigen presentation.     

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)     

Expression of the CD54 (ICAM-1) and CD11 a (LFA-1) adhesion molecules in oral mucosal inflammation

Previous studies of chronic dermatoses have suggested that expression of the CD54 cell surface antigen (intercellular adhesion molecule-1, ICAM-1) by keratinocytes is a feature of chronic inflammation. However, whether such expression is a prerequisite for intraepithelial migration of lymphocytes is unclear. The present study evaluated the expression of CD54 and its ligand, CD1 la (lymphocyte function-associated antigen, LFA-1) in oral lesions of lichen planus, recurrent aphthous stomatitis, secondary Sjögren's syndrome and traumatic ulceration using an immunoperoxidase technique. In 33 of 56 lesions examined, substantial numbers of CD1 la + cells were present within oral mucosal epithelium despite an absence of detectable keratinocyte CD54 antigen expression. Consequently, CD54/CD1 la adhesion interactions may not be critical in the initiation of oral mucosal inflammation.     

VCAM-1 and ICAM-1 are expressed by Langerhans cells, macrophages and endothelial cells in oral lichen planus

Expression of intercellular adhesion molecule-1 (ICAAM-1, CD54) and vascular cell adhesion molecule-1 (VCAM-l, CD106) was examined in oral lichen planus (OLP) and normal oral mucosa (NOM). Immunoperoxidase staining showed ICAM-1 expression by vascular endothelium in all biopsies of OLP and NOM whereas endothelial VCAM-l staining was found in 2/7 NOM and 8/9 OLP. In the lamina propria of NOM occasional cells were ICAM-1 or VCAM-l positive, and virtually no staining of intraepilhelial dendritic cells was seen for either marker. Intraepithelial dendritic cells stained for ICAM-1 in 7/9 and VCAM-1 in 4/9 OLP biopsies. Double immunofluorescence showed dual labelling of Langerhans cells (LC) with CD1a and VCAM-l in a further 5/12 cases of OLP, but there was no such staining in four NOM. This is the first report of LC staining with VCAAM-l. Induction of ICAM-1 and VCAM-l on LC and macrophages in OLP suggests these cells are activated and may contribute to the pathogenesis of OLP by presenting antigen to infiltrating lymphocytes.     

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.     

Pathogenesis of oral lichen planus – a review

J Oral Pathol Med (2010) 39 : 729–734 Oral lichen planus (OLP) is a T‐cell‐mediated chronic inflammatory oral mucosal disease of unknown etiology. OLP presents as white striations, white papules, white plaques, erythema, erosions, or blisters affecting predominantly the buccal mucosa, tongue and gingiva. Both antigen‐specific and non‐specific mechanisms are hypothesized to be involved in the pathogenesis of oral lichen planus (OLP). Antigen‐specific mechanisms in OLP include antigen presentation by basal keratinocytes and antigen‐specific keratinocyte killing by CD8⁺ cytotoxic T cells. Non‐specific mechanisms include mast cell degranulation and matrix metalloproteinase activation in OLP lesions. These mechanisms may combine to cause T cell accumulation in the superficial lamina propria, basement membrane disruption, intra‐epithelial T cell migration and keratinocyte apoptosis in OLP. The various hypotheses proposed for pathogenesis of oral lichen planus are discussed in this review.