Identification of inflammatory cell phenotypes in human oral carcinomas by means of monoclonal antibodies

Monoclonal antibodies reacting with human T cell sub-populations, Langerhans cells and macrophages were used to examine the quantitative distribution of immune-competent cells in normal oral mucosa and invasive oral carcinomas. Both immunofluorescent and immunoperoxidase procedures were applied. In normal oral epithelia, the dominant immune-reactive cell was the Langerhans cell, positive for OKT 6 and expressing HLA-DR gene products (OKIal⁺). Many intra-epithelial non-epithelial cells (non-keratinocytes), belonged to the lymphocyte system carrying the suppressor/cytotoxic phenotype (OKT 8⁺). This lymphocyte sub-population was also the most prominent cell type in the normal mucosal stroma. The quantitative evaluation of immune-competent cells in squamous cell carcinomas revealed elevated numbers of all the inflammatory cell sub-populations investigated (suppressor/cytotoxic lymphocytes, helper/inducer lymphocytes, Langerhans cells, macrophages) compared with the normal oral mucosa. There was a striking increase in suppressor/cytotoxic lymphocytes (OKT 8⁺) and in cells of the macrophage system, including Langerhans cells (OKIal⁺, OKM l⁺, OKT 6⁺). In the stroma distant to the tumour complexes, many helper/inducer lymphocytes (OKT 4⁺) were also observed.     

Pattern of distribution of T lymphocytes, Langerhans cells and HLA-DR bearing cells in normal human oral mucosa

The tissue distribution of helper/inducer and suppressor/cytotoxic T cells, Langerhans cells (LC) and HLA-DR bearing cells was determined in normal oral mucosa by use of monoclonal antibodies OKT4, OKT8, OK.T6 and OKIal, respectively. OKT4+ and OKT8+ cells were invariably present in normal oral epithelium and in the lamina propria. OKT8+ cells were consistently seen inside the basal cell layer of the epithelium. The distribution of LC in oral epithelium showed regional variation. In palatal epithelium LC were evenly distributed in the basal half of the epithelium, whereas in buccal mucosa the highest concentration of LC was seen in the epithelium overlying the tips of connective tissue papillae. OKIal stained dendritic cells in the epithelium and plump cells with small dendritic processes in the connective tissue. Some of the latter were located close to the basal cells of the epithelium. The consistent relationship between immunocompetent cells and the epithelium of the oral mucosa suggests the presence of a local immunologic defence barrier in the oral mucosa.     

Pattern of distribution of T lymphocytes, Langerhans cells and HLA-DR bearing cells in normal human oral mucosa

The tissue distribution of helper/inducer and suppressor/cytotoxic T cells, Langerhans cells (LC) and HLA-DR bearing cells was determined in normal oral mucosa by use of monoclonal antibodies OKT4, OKT8, OKT6 and OKIa1, respectively. OKT4+ and OKT8+ cells were invariably present in normal oral epithelium and in the lamina propria. OKT8+ cells were consistently seen inside the basal cell layer of the epithelium. The distribution of LC in oral epithelium showed regional variation. In palatal epithelium LC were evenly distributed in the basal half of the epithelium, whereas in buccal mucosa the highest concentration of LC was seen in the epithelium overlying the tips of connective tissue papillae. OKIa1 stained dendritic cells in the epithelium and plump cells with small dendritic processes in the connective tissue. Some of the latter were located close to the basal cells of the epithelium. The consistent relationship between immunocompetent cells and the epithelium of the oral mucosa suggests the presence of a local immunologic defence barrier in the oral mucosa.     

Dyskeratosis in human and experimental oral precancer and cancer. An immunohistochemical and ultrastructural study in men, mice and rats

Dyskeratotic cells were examined with light and electron microscopy in human oral leukoplakias and carcinomas and in chemically-induced oral premalignant and malignant lesions of mice and rats. Specific antisera against small and large keratins were used to analyse the distribution of keratin polypeptides. In normal oral mucosa, basal cells did not react with antibodies against large keratins in contrast to the suprabasal cells which did react. Small keratins were found in all epithelial cell layers. In human and experimental premalignant and malignant lesions, intensely labelled dyskeratotic cells were seen, which contained small and large keratins regardless of their position in the epithelium. At the ultrastructural level, these cells showed dense aggregates of tonofilaments. Dyskeratotic cells were often seen in advanced stages of degeneration of phagocytosis of these cells by macrophages and giant cells was frequent. The disturbance of the keratinization process in oral precancer and cancer is easily visualized using keratin antisera. Keratin analysis can give new insights in epithelial maturation and may be helpful for the classification of oral leukoplakia.     

Extent and diversity of inflammatory cell infiltrates in squamous cell carcinomas and basal cell epitheliomas of the head and neck

Using monoclonal antibodies reactive with Langerhans' cells (LCs), macrophages, and T cell subpopulations, the density and proportions of cells of the immune system of the normal oral mucosa were determined immunohistochemically, and compared with findings in oral squamous cell carcinomas (SCC) and basal cell epitheliomas (BCE). In normal oral epithelia, the dominant cell type was the LC, positive for CD 1, and expressing HLA-DR antigens (DR+). Many intraepithelial cells were lymphocytes of the suppressor/cytotoxic phenotype (CD 8+), which was also the most prominent cell type in the normal mucosal stroma. Significant differences were observed for the content of CD 8-, OKM 1-, and CD 4-positive cells in the epithelium of normal oral mucosa, SCC, and BCE, and for the amount of CD 1-positive Langerhans cells in the connective tissue of the different groups of tissues. When CD 4/CD 8 ratios were calculated, differences between SCC and BCE became most evident. A CD 4/CD 8 ratio greater 0.5 was seen to be characteristic for BCE. Thus, in contrast to the striking preponderance of suppressor/cytotoxic lymphocytes (CD 8+) in SCC, BCE showed typically almost balanced numbers of suppressor/cytotoxic (CD 8+) and helper/inducer (CD 4+) lymphocytes. This finding further underlines the biological differences recognized between these most common neoplasias of the head and neck.     

Extent and diversity of inflammatory cell infiltrates in squamous cell carcinomas and basal cell epitheliomas of the head and neck

Using monoclonal antibodies reactive with Langerhans' cells (LCs), macrophages, and T cell subpopulations, the density and proportions of cells of the immune system of the normal oral mucosa were determined immunohistochemically, and compared with findings in oral squamous cell carcinomas (SCC) and basal cell epitheliomas (BCE). In normal oral epithelia, the dominant cell type was the LC, positive for CD 1, and expressing HLA-DR antigens (DR⁺). Many intraepithelial cells were lymphocytes of the suppressor/cytotoxic phenotype (CD 8⁺), which was also the most prominent cell type in the normal mueosal slroma. Significant differences were observed for the content of CD 8-, OKM 1-, and CD 4-positive cells in the epithelium of normal oral mucosa, SCC, and BCE, and for the amount of CD 1-positive Langerhans cells in the connective tissue of the different groups of tissues. When CD 4/CD 8 ratios were calculated, differences between SCC and BCE became most evident. A CD 4/CD 8 ratio greater 0.5 was seen to be characteristic for BCE. Thus, in contrast to the striking preponderance of suppressor/cytotoxic lymphocytes (CD 8⁺) in SCC, BCE showed typically almost balanced numbers of suppressor/cytotoxic (CD 8⁺) and helper/induced (CD 4⁺) lymphocytes. This finding further underlines the biological differences recognized between these most common neoplasias of the head and neck.     

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.     

Langerhans cells in oral epithelium of chronically inflamed human gingivae

This study describes the histopathological features and the distribution of oral epithelial Langerhans cells in 19 gingival biopsies originating from an adult Tanzanian population characterized by very poor oral hygiene and severe gingival inflammation. Light-microscopically, all biopsies contained often large inflammatory connective tissue infiltrates, 6 of which predominantly contained plasma cells while the rest were dominated by lymphocytes. Seven specimens contained peculiar accumulations of round lymphoid and dendritic cells in the lower cell layers of the oral epithelium. These phenomena have not previously been demonstrated in human gingiva and deserve further attention in studies on the pathogenesis of periodontal diseases. Immuno-histochemical staining with OKT6, OKT4 and OKT8 antibodies showed markedly increased numbers of OKT6-positive cells in 7 specimens and clusters of OKT4- and OKT8-positive cells in the oral epithelium of 4 specimens. High numbers of OKT6-positive cells were not related to the presence of intra-epithelial, non-keratinocyte infiltrates or large connective tissue infiltrates. The variable numbers of oral epithelial Langerhans cells may therefore result from different bacterial antigens elucidating different responses or, alternatively, reflect different responses to similar plaque antigens penetrating the surface of the oral epithelium.     

An immunohistochemical study of oral submucous fibrosis

Oral submucous fibrosis (OSF) is a chronic disease of the oral cavity characterized by inflammation and progressive mucosal fibrosis. These reactions may be the result of either direct stimulation from exogenous antigens like areca alkaloids or by changes in tissue antigenicity that may lead to an autoimmune response. This study investigated the presence and distribution of inflammatory cells and MHC class II antigen expression by epithelial and immunocompetent cells using a three-stage immunoperoxidase method on frozen sections. Thirty OSF tissue specimens and ten normal buccal mucosae were studied and compared. All tissues were investigated using antibodies to T cells (CD3), T helper/inducer cells (CD4), T suppressor/cytotoxic cells (CD8), B cells (CD20), naive T cells and monocytes (CD45RA), macrophages. Langerhans' cells (CD68) and HLA-DR-positive cells (HLA-DR alpha). The predominant cell populations detected in normal tissues were CD3, CD4 and HLA-DR-positive cells. The distribution of CD4-positive cells was similar to that of CD3-positive cells, which were scattered, often uniformly distributed, both in the epithelium and connective tissue. CD8-positive cells were occasionally seen in the normal epithelium and lamina propria. Few scattered B cells (CD20) and macrophages (CD681) were observed in normal mucosa. Naive T cells (CD45RA) were seen in all normal tissues focally concentrated around the connective tissue papillae with a similar distribution to that of CD3-positive cells. All normal sections showed HLA-DR-positive cells scattered both in the epithelium and in the lamina propria. Epithelial cells did not show any positive reaction to this antibody and many intraepithelial positive cells showed a dendritic morphology. The cell populations detected in OSF showed higher numbers of CD3 and HLA-DR-positive cells compared with those of the normal tissues. The pattern of staining for CD4-positive cells in OSF tissues was similar to that of CD3-positive cells both in the epithelium and connective tissue and was higher than that in normal tissues. A few scattered CD8-positive cells and only occasional CD20- and CD68-positive cells were seen in OSF sections. Few CD45RA-positive cells were found in the epithelium and lamina propria of OSF sections. However, OSF specimens showed high numbers of HLA-DR-positive cells in the basal layer of the epithelium, juxtaepithelium and in the lamina propria in a similar distribution to that of CD3 cells compared with the normal tissues. Most HLA-DR-positive cells in the epithelium showed dendrites directed vertically towards the surface. The increased evidence of CD4 and HLA-DR-positive cells in OSF tissues suggests that most lymphocytes were activated and shows an increased presence of Langerhans' cells. The presence of these immunocompetent cells and high ratio of CD4 to CD8 in OSF tissues suggest an ongoing cellular immune response leading to a possible imbalance of immunoregulation and alteration in local tissue architecture.     

Quantification and distribution of lymphocyte subsets and Langerhans cells in normal human oral mucosa and skin

Normal human oral (check) mucosa was studied to discover whether the oral cavity resembles the Mucosal Immune System (MIS) or the Skin Immune System (SIS). Immunophenotypes of lymphocyte subsets and Langerhans cells (LC) with their exact locations in the epithelium and papillary layer of the normal buccal mucosa were determined and compared with data of normal human skin. In a double staining procedure, the distribution of T-lymphocytes in relation to blood and lymph vessels was determined. Immunophenotyping of LC was done with a CD1a monoclonal antibody. In contrast to the skin, T-lymphocytes in buccal mucosa are not primarily perivascular in location. They are more or less randomly distributed on both sides of the basement membrane. The epithelium of the buccal mucosa contains about 37 times as many T-lymphocytes as the epidermis of normal skin. T-cell numbers in the papillary layer are more or less comparable. The CD4/CD8 ratios of about 1/2 in the epithelium of buccal mucosa and 1/4 in the skin indicates preferential presence of the CD8 subset in both sites, but the helper/inducer T-lymphocytes play a much greater role in the epithelium of the buccal mucosa when compared with skin. B-lymphocytes were not found in the epithelium and papillary layer of the buccal mucosa. Thus, immune response associated cells in buccal mucosa do not show the MIS pattern since B cells are absent. It has more in common with SIS but differences are also apparent. In the epithelium of the buccal mucosa the density of LC does not differ significantly from that of the skin, but the papillary layer of the buccal mucosa contains significantly fewer LC than the skin. As in the skin most of the LC of the buccal mucosa are found in the epithelium.     

Occurrence of papillomavirus structural antigens in oral papillomas and leukoplakias

Six oral papillomas and 7 oral leukoplakias were studied with genus-specific antibodies against detergent-disrupted papillomaviruses. Indirect immunofluorescence staining was applied to frozen sections. Distinct nuclear staining of superficial keratinocytes was seen in 5 of 6 oral papillomas, 2 of 5 homogenous leukoplakias, and in 2 cases of nodular leukoplakia, one of these showing transition into an invasive carcinoma. Papillomavirus antibodies offer a new way to detect and localize papillomaviruses in epithelial hyperplasias. The relevance of the immunomorphological identification of papillomavirus-associated antigens is discussed with special reference to the molecular hybridization technique.     

Occurrence of papillomavirus structural antigens in oral papillomas and leukoplakias

Six oral papillomas and 7 oral leukoplakias were studied with genus-specific antibodies against detergent-disrupted papillomaviruses. Indirect immunofluorescence staining was applied to frozen sections. Distinct nuclear staining of superficial keratinocytes was seen in 5 of 6 oral papillomas, 2 of 5 homogenous leukoplakias, and in 2 cases of nodular leukoplakia, one of these showing transition into an invasive carcinoma. Papillomavirus antibodies offer a new way to detect and localize papillomaviruses in epithelial hyperplasias. The relevance of the immunomorphological identification of papillomavirus-associated antigens is discussed with special reference to the molecular hybridization technique.     

Immunocytochemical examination of immune cells in periapical granulomata and odontogenic cysts

Monoclonal antibodies (mAbs) were used to determine the presence and distribution of immune cells including lymphocytes, macrophages and Langerhans cells, in normal periodontal ligament, periapical granulomata, periapical cysts and dental developmental cysts. Isolated T-lymphocytes, but not B-lymphocytes, were detected in specimens of non-inflamed periodontal ligament. Increased numbers of T and B lymphocytes were found in all of the lesions examined. Monocytes/macrophages were associated with most periapical granulomata, dental developmental cysts and all periapical cysts. Langerhans cells, intraepithelial lymphocytes, and monocytes/macrophages were not detected in the rests of Malassez but were found in some epithelia within periapical granulomata and in most epithelial linings of odontogenic cysts. Increased numbers of immune cells were seen around proliferative epithelia and adjacent to the epithelial linings of cysts. Epithelium, particularly that of odontogenic cysts, showed positive reactions for HLA-Dr, lysozyme and for α-1 antitrypsin. The presence of immune cells in periapical granulomata and odontogenic cysts, suggests that cell-mediated and humoral immunoreactions occur in these lesions and may be associated with the epithelial proliferation within the periapical lesions.     

In situ characterization of mononuclear cells in human chronic marginal periodontitis using monoclonal antibodies

Acetone fixed cryostat sections from 25 patients with adult chronic marginal periodontitis were characterized using an indirect immunofluorescence technique with monoclonal antibodies. The amount of B lymphocytes (Leu-12 positive) varied considerably between the specimens and were usually seen in largest numbers in the most apical parts of the cellular infiltrates beneath the pocket epithelium (PE). Varying amounts of T lymphocytes (OKT 3 positive) were demonstrated in all specimens. The amount of T helper cells (OKT 4a positive) exceeded that of T suppressor/cytotoxic cells (OKT 8 positive) in the cellular infiltrates beneath the PE (OKT 4a/ OKT 8 =1.13). There was a more even distribution of these cell types beneath the oral gingival epithelium (OGE). Langerhans cells were observed within and occasionally subjacent to the OGE. Scattered macrophages (Leu-M3 or OK Ia 1 positive) were observed in the inflammatory cell infiltrates and on the connective tissue papillae beneath the OGE. HLA-DR antigen reacting with OK Ia 1 was present on cells corresponding to OKT 6 positive cells in the OGE and subjacent to the OGE as well as in the inflammatory cell infiltrates beneath the PE and in the perivascular infiltrates. In some specimens HLA-DR antigen was also found to be associated with keratinocytes in the outer parts of the OGE. Occasional NK cells (Leu-7 positive) were localized inside and subjacent to the OGE. There was a considerable variation with respect to the number and distribution of the various mononuclear cells between specimens and from section to section from the same specimen.     

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.     

Characterisation of the inflammatory cell infiltrate in chronic hyperplastic candidosis of the oral mucosa

The inflammatory cell infiltrate in biopsy material of chronic hyperplastic candidosis (CHC) from the oral mucosa was characterised using immunocytochemical techniques. Nine specimens were stained for human kappa and lambda immunoglobulin light chains. CD68 antigen (macrophages), lysozyme (macrophages, granulocytes), CD3 antigen (T-lymphocytes), CD20 antigen (B-lymphocytes) and leucocyte common antigen (LCA). In addition, these and a further 13 specimens were also examined for immunoglobulin (Ig)-containing cells (IgA, IgG and IgM). The density of the infiltrate varied considerably between cases: T-lymphocytes were the dominant cell type (153.9%), with fewer B-lymphocytes (8.2%) and macrophages (14.2%). Many Ig-containing cells were seen, and although IgG-containing cells predominated, (60.8%, SD ±9.0) there was a high proportion of IgA-containing cells (36.7%, SD ± 9.1) with few IgM-containing cells (2.5%, SD ±3.0). Many neutrophils, together with smaller numbers of T-lymphocytes and macrophages were seen in the epithelium. It is suggested that mucosal defence to Candida infection involves a cell-mediated reaction in which there is recruitment of macrophages and local production of immunoglobulin with a prominent IgA component.     

T-lymphocyte and Langerhans cell distribution in normal and allergically induced oral mucosa in contact with nickel-containing dental alloys

An in vivo comparison was made between the contact allergic stomatitis-inducing capacity of nickel, nickel-containing dental alloys and a non-corrosive precious metal. Fifteen patients with a positive allergic skin reaction to nickel were divided into 3 groups (A, B and C). The patients in Group A (n = 4) were fitted with an intra-oral corrosion-resistant nickel-chromium Alloy A; the patients of Group B (n = 5) received a more corrosion prone nickel-chromium Alloy B and in Group C (n = 6) strongly corroding pure nickel was used. A corrosion-resistant foil of pure palladium was placed on the contralateral side. Reactivity of pure nickel foil was also tested on the skin in Group C. Immunohistological examination of the oral mucosa on the test and reference sides was performed with monoclonal antibodies directed against T-lymphocyte subsets and Langerhans cells (LC). The results showed that at the pure nickel site the LC did increase significantly in the connective tissue (approx. 4X) of the oral mucosa. However, statistical analysis of all 6 patients of Group C together showed no corresponding increase of LC in the epithelium at the site with the pure nickel, although a numerical increase of LC was noted in the epithelium adjacent to the pure nickel foil in 2 patients, which was remarkable. It can be concluded from statistical analysis that both the reference foils and the test foils can influence the number of suppressor/cytotoxic T-lymphocytes in the connective tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oral lichen planus: characterization of immunocompetent cells with hybridoma antibodies

Monoclonal antibodies which react against T-cell subpopulations and Langerhans' cells were used to examine the phenotype of immunocompetent cells in oral lichen planus. Immunomorphologically, the stromal infiltrate of this condition considerably resembled the delayed type of immune reaction. Although all subpopulations of immunocompetent cells were present in the stromal infiltrate, Langerhans' cells (OKT-6 positive, HLA-DR positive) and suppressor/cytotoxic T-lymphocytes (OKT-3 positive, OKT-4 negative, OKT-8 positive, HLA-DR positive) predominated. Our immunohistological findings support the suggestion that aggregations of T-lymphocytes are responsible for the cytotoxic processes which occur within the squamous epithelium in oral lichen planus.     

Expression of Class II transplantation antigens by epithelial cells in oral candidosis, oral lichen planus and gingivitis

Biopsies from normal oral mucosa and oral mucosa affected by candidosis, lichen planus or gingivitis were compared with respect to the expression of two Class II transplantation antigens, HLA-DR and HLA-DQ, by epithelial cells and the relationship of these antigens to the distribution and frequency of T-lymphocytes. Indirect immunohistochemistry with different mouse monoclonal antibodies was used on frozen and acetone-fixed sections. To evaluate the results, a score system based upon the expression of the Class II transplantation antigens by epithelial cells and the frequency of T-lymphocytes was used. In oral candidosis there was a marked expression of HLA-DR antigens throughout the epithelium. In addition, this type of epithelium was the only one that expressed HLA-DQ antigens. An intense intraepithelial infiltration of T-lymphocytes was observed. Oral lichen planus and gingivitis did, to a much lesser extent, cause the expression HLA-DR antigens by the epithelial cells. In both lesions, the number of T-lymphocytes within the epithelium did not exceed the number found in epithelium of normal mucosa. In these types of lesions, the subepithelial infiltrate varied in intensity but was mainly composed of T-lymphocytes reactive with anti-Leu 3a antibodies. The results of the present study imply that epithelial expression of the two different Class II antigens are related to the frequency of the T-lymphocytes and to the proximity of these cells to the epithelial cells.