Bengt Hasséus

Langerhans cells and T cells in oral graft versus host disease and oral lichen planus.

Chronic graft versus host disease (cGVHD) of the oral mucosa, following allogeneic stem cell transplantation, and oral lichen planus (OLP) are both mucosal diseases where the immune system is involved in the pathogenesis. Although the aetiology of the two conditions is different, they present with a similar clinical appearance. This study compares the two diseases regarding the distribution of cells, which are expressing cell surface markers of interest for inflammatory responses. Monoclonal antibodies (MoAbs) were used in standard immunohistochemical procedures. CD1a+, CD80+ and CD86+ cells in the epithelium of OLP‐ and cGVHD lesions had the dendritic morphology of Langerhans cells (LC). Higher frequencies of CD1a+ LC as well as CD25+ cells were observed in the OLP epithelium than in the cGVHD epithelium. The OLP lesions showed higher frequencies of subepithelial cells expressing CD1a, CD86, CD4, CD8 and CD25 than the cGVHD lesions. Notably there was a significantly higher frequency of CD25+ cells in the epithelium and the connective tissue of OLP than in cGVHD. These cells might represent regulatory T cells. In conclusion, cGVHD and OLP show marked differences at the cellular level despite similar clinical appearance. Hence, the findings indicate differences in the regulation of the inflammatory response between the two conditions.

Langerhans Cells from Oral Epithelium are More Effective in Stimulating Allogeneic T-cells in vitro than Langerhans Cells from Skin Epithelium

Dendritic cells, such as Langerhans cells (LC), in different ectodermal compartments may have different functional capabilities. The present study was undertaken to compare oral Langerhans cells (LC) with those of the epidermis in terms of their ability to co-stimulate T-cells in vitro. A Mixed Epithelial Cell Lymphocyte Reaction (MELR) and a mitogen-driven (concanavalin A) T-cell proliferation assay were used. In both assays, LC in a crude cell suspension of freshly isolated oral epithelial cells were found to be five times more effective in mediating T-cell proliferation than freshly isolated epidermal LC. Twenty-four-hour cell culture at 37°C enhanced the T-cell response in the MELR compared with cells cultured at 4°C. This applied to both skin and oral epithelial cells. Oral and skin epithelial cell suspensions depleted of LC lost the capacity to stimulate allogeneic T-cells. Incubation of the epithelial cell suspensions with recombinant Granulocyte/Macrophage-Colony Stimulating Factor (rGM-CSF) did not enhance the co-stimulating capacity of the LC. Titration of different numbers of oral and skin LC to T-cells showed that skin LC were never able to reach more than 44% of the maximal stimulatory capacity of oral LC. Data show that oral LC are more efficient than skin LC in providing co-stimulatory signals to T-cells, suggesting a difference in functional capacity between the two cell populations.

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.

Langerhans Cells and T Cells Sense Cell Dysplasia in Oral Leukoplakias and Oral Squamous Cell Carcinomas – Evidence for Immunosurveillance

Leukoplakias (LPLs) are lesions in the oral mucosa that may develop into oral squamous cell carcinoma (OSCC). The objective of this study was to assess presence and distribution of dendritic Langerhans cells (LCs) and T cells in patients with LPLs with or without cell dysplasia and in oral squamous cell carcinoma (OSCC). Biopsy specimens from patients with leukoplakias (LPLs) with or without dysplasia and oral squamous cell carcinoma (OSCC) were immunostained with antibodies against CD1a, Langerin, CD3, CD4, CD8 and Ki67, followed by quantitative analysis. Analyses of epithelium and connective tissue revealed a significantly higher number of CD1a + LCs in LPLs with dysplasia compared with LPLs without dysplasia. Presence of Langerin + LCs in epithelium did not differ significantly between LPLs either with or without dysplasia and OSCC. T cells were found in significantly increased numbers in LPLs with dysplasia and OSCC. The number of CD4+ cells did not differ significantly between LPLs with and without dysplasia, but a significant increase was detected when comparing LPLs with dysplasia with OSCC. CD8+ cells were significantly more abundant in OSCC and LPLs with dysplasia compared with LPLs without dysplasia. Proliferating cells (Ki67+) were significantly more abundant in OSCC compared to LPLs with dysplasia. Confocal laser scanning microscopy revealed colocalization of LCs and T cells in LPLs with dysplasia and in OSCC. LCs and T cells are more numerous in tissue compartments with dysplastic epithelial cells and dramatically increase in OSCC. This indicates an ongoing immune response against cells with dysplasia.

Oral medicine (stomatology) across the globe: Birth, growth, and future

Oral medicine (stomatology) is a recognized and increasingly important dental specialty in many parts of the world that recognizes and fosters the interplay between medical health and oral health. Its dental activities rely greatly on the underlying biology of disease and evidence-based outcomes. However, full recognition of the importance of oral medicine to patient care, research, and education is not yet totally universally acknowledged. To address these shortcomings, we outline the birth, growth, and future of oral medicine globally, and record identifiable past contributions to the development of the specialty, providing an accurate, unique, and valuable resource on oral medicine. Although it was challenging to gather the data, we present this information as a review that endeavors to summarize the salient points about oral medicine, based on MEDLINE, other internet searches, communication with oral medicine and stomatological societies across the world, the web page http://en.wikipedia.org/wiki/List_of_dental_organizations, and discussions with a wide range of key senior persons in the specialty.

Estren promotes androgen phenotypes in primary lymphoid organs and submandibular glands

BackgroundEstrogens and androgens have extensive effects on the immune system, for example they suppress both T and B lymphopoiesis in thymus and bone marrow. Submandibular glands are sexually dimorphic in rodents, resulting in larger granular convoluted tubules in males compared to females. The aim of the present experiments was to investigate the estrogenic and androgenic effects of 4-estren-3α,17β-diol (estren) on thymus, bone marrow and submandibular glands, and compare the effects to those of 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT), respectively. Estrogen receptors (ERs) were blocked by treatment of mice with the ER-antagonist ICI 182,780; also, knock-out mice lacking one or both ERs were used.ResultsAs expected, the presence of functional ERs was mandatory for all the effects of E2. Similar to DHT-treatment, estren-treatment resulted in decreased thymus weight, as well as decreased frequency of bone marrow B cells. Treatment with estren or DHT also resulted in a shift in submandibular glands towards an androgen phenotype. All the effects of estren and DHT were independent of ERs.ConclusionOur study is the first to show that estren has similar effects as the androgen DHT on lymphopoiesis in thymus and bone marrow, and on submandibular glands, and that these effects are independent of estrogen receptors. This supports the hypothesis of estren being able to signal through the androgen receptor.

Oral and lip cancer in solid organ transplant patients--a cohort study from a Swedish Transplant Centre.

OBJECTIVES Previous large studies have shown that solid organ transplant (SOT) patients have an increased risk of developing malignancies. Few studies have compared the prognosis for SOT patients who develop cancer with that of non-transplanted cancer patients. In this study we have investigated the increased risk of oral and lip cancer in SOT patients and also compared the relative survival between SOT patients and non-SOT patients with oral and lip cancer. PATIENTS AND METHODS From the patient registers at the Transplant Institute at Sahlgrenska University Hospital, records of 4604 SOT patients from 1965 to 2010 were collected. These patient records were linked to the nationwide Swedish Cancer Register and compared to those of the normal population regarding the risk of developing oral and lip cancer, and also to non-SOT patients with lip and oral cancer. A Poisson regression model was used to compare the relative survival between SOT and non-SOT patients with oral and lip cancer. RESULTS We observed 17 oral cancers (expected 2.69) and 34 lip cancers (expected 0.78) in the cohort. The standardized incidence ratio (SIR) for oral cancer was 6.32 (95% CI, 3.7-10.1) and 43.7 (95% CI, 30.3-61.1) for lip cancer. Relative five-year survival for lip cancer was lower for SOT patients compared to non-SOT patients (p<0.001). CONCLUSION This study shows that SOT patients have a higher risk of developing both oral and lip cancer, and in addition, that SOT patients with lip cancer have a worse prognosis.

Partially erupted third molars as a potential source of infection in patients receiving peripheral stem cell transplantation for malignant diseases: a retrospective study.

Forty-four patients with malignant diseases for which they received peripheral stem cell transplant therapy (PSCT) were retrospectively studied regarding local and systemic infection originating from around partially erupted third molars (PEMs). Twenty-two patients had one or more PEMs, while 22 patients had none. Data were retrieved from medical and dental records. Systemic and local signs of infection and treatment were assessed. We recorded the number of transplanted CD34(+) blood stem cells, days with white blood cell counts < 0.5 x 10(9) l(-1), days until engraftment, maximum level of C-reactive protein (CRP), days with fever, positive blood cultures, days taking antibiotics, days drinking < 0.5 l, days of total parenteral nutrition, days receiving intravenously administered analgesics, and number of admission days. No statistically significant difference was detected between patients with PEMs and those without PEMs regarding any of the studied parameters. Of patients with PEMs, 36% (8 of 22) developed local infections around PEMs during the PSCT period. The study indicates that PEMs pose no significant risk of causing systemic infection in patients receiving PSCT for malignant diseases but increase the risk of developing a local infection, justifying close supervision and early treatment in cases of local infection during PSCT treatment.

Does Crohn's Disease with Concomitant Orofacial Granulomatosis Represent a Distinctive Disease Subtype?

Background:Although orofacial granulomatosis (OFG) may present as a separate clinical entity, it often seems in conjunction with various systemic diseases, of which Crohns disease (CD) is one of the most common. The aim of this study was to investigate whether CD with concomitant OFG represents a distinctive disease subtype. Methods:Twenty-one patients with CD and concomitant OFG (CD+OFG group) were included in the study. As the reference group, a cohort of 39 patients with CD but without OFG (CD-R group) was used. Demographic data and clinical characteristics were recorded at the time of diagnosis. The 2 groups were compared using multivariate analyses. Results:The percentage of patients with intestinal inflammation in the upper gastrointestinal tract was significantly higher in the CD+OFG group, as compared with the CD-R group (81% versus 33%; P < 0.001). Furthermore, ileocolonic inflammation was significantly more common in the CD+OFG patients (81% versus 46%; P = 0.013). In addition, perianal disease was more frequently observed in the CD+OFG group (48% versus 18%; P = 0.033). Significantly more patients showed evidence of granulomas in the primary endoscopy in the CD+OFG group than in the CD-R group (81% versus 38%; P = 0.003). Conclusion:The data from this study suggest that the presence of CD in conjunction with OFG represents a distinctive subphenotype of CD that is characterized by extensive inflammation, perianal disease, and pronounced granuloma formation in the intestine.

Immunophenotype in orofacial granulomatosis with and without Crohn's disease.

Objectives: The aim of this investigation was to characterise and compare the inflammatory infiltrates in patients with orofacial granulomatosis solely (OFG-S) and OFG with coexisting Crohn’s disease (OFG+CD). Study Design: Biopsy specimens with granulomas were obtained from patients with OFG-S (n=11) and OFG+CD (n=11) and immunostained with antibodies against CD1a, CD3, CD4, CD8, CD11c, CD20, CD68 and mast cell tryptase, followed by quantitative analysis. Results: Analyses of the connective tissue revealed a significantly higher number of CD3-expressing T cells and CD11c-expressing dendritic cells in the connective tissue of patients with OFG-S compared to patients with OFG+CD. Mast cells displayed a high level of activation, although no significant difference was detected when comparing the two groups. Conclusions: The results show a different composition of the inflammatory infiltrate in patients with OFG-S compared to patients with OFG+CD. The present observations support that partly divergent immune mechanisms are involved in these two different subcategories of OFG. Key words:Granulomas, autoimmunity, T cells, B cells, dendritic cells, children, adults.