Langerhans cells in oral mucosa and skin. A functional and morphological study

Abstract

Langerhans cells (LC) are a subpopulation of dendritic cells residing in skin and mucosal epi-thelium. LC capture antigens in the periphery and following migration to regional lymph nodes present peptides to T cells. LCs have a central role in initiating a T cell mediated immune re-sponse, both in health and disease. This thesis has focused on the capacity of rodent and human oral and skin MHC class II expressing LC to stimulate T cells in vitro. Assessment of cytokine production (IFNg and IL-8) in cultures has been done. Further on, distribution and morphology of LC and T cells in biopsies from patients with oral lichen planus or graft versus host disease have been analysed. Rodent and human oral and skin specimens were obtained, and single cell suspensions were prepared after enzymatic treatment. Rodent lymph nodes or human venous blood were collected, and purified T cells were prepared by monoclonal antibodies and immunomagnetic beads. Oral or skin epithelial cells including LC were cocultured with syngeneic con A stimulated T cells or allo-geneic T cell in Mixed Epithelial Cell Lymphocyte Reactions. MHC class II molecule expression was assessed by immunohistochemistry and flow cytometry and cytokine production by ELISA. In human oral mucosa and skin CD1a expressing LC were enumerated. Fresh rodent oral MHC class II expressing LC have the ability to generate accessory signals to T cells and serve as antigen presenting cells. Rodent and human oral LC were more efficient in stimulating allogeneic T cells than skin LC in Mixed Epithelial cell Lymphocyte Reactions. IFNg was produced in higher amounts in cell cultures with oral epithelial cells and allogeneic T cells than in corresponding cultures with skin epithelial cells. A soluble factor with suppressive activity is produced in cultures of skin epithelial cells and allogeneic T cells, as demonstrated in experiments with shifting of supernatants from cultures of oral epithelial cells and allogeneic T cells to cultures of skin epithelial cells and allogeneic T cells and vice versa. MHC class II molecule expression on oral and skin epithelial cells, following cul-ture, differ with respect to a population of brightly stained oral epithelial cells that were not found among skin epithelial cells. These populations most likely represent LC. CD1a+ LC were present in higher frequencies in oral lichen planus lesions than in chronic graft versus host disease lesions. The frequencies of CD4+ and CD8+ cells in the inflammatory infiltrate of oral lichen planus lesions were higher than in chronic graft versus host disease lesions. Notably, CD4+/CD25+ cells were present in higher frequency in the inflammatory infiltrates of oral lichen planus than in infiltates of chronic graft versus host disease. These cells may represent regulatory T cells contributing to the clinical similarity between the two diseases despite the marked differences in inflammatory infiltrates.