Ratio of Langerhans Cells to Thy-1+ Dendritic Epidermal Cells in Murine Epidermis Influences the Intensity of Contact Hypersensitivity

Abstract

We have initiated a series of studies in vivo to investigate the physiologic role of Langerhans cells and Thy-1+ dendritic epidermal cells in the development and regulation of contact hypersensitivity. The density of I-A+ Langerhans cells and Thy-1+ dendritic epidermal cells in ammonium thiocyanate-separated epidermal sheets was determined in ten strains of inbred mice using immunofluorescence microscopy with monoclonal anti-I-A and anti-Thy-1 antibodies. Mice of different inbred strains were sensitized by painting the left ear with varying doses of either oxazolone or trinitrochlorobenzene. From five to 20 days after sensitization, groups of mice were challenged with the relevant antigen and the intensity of contact hypersensitivity, as measured by ear swelling, was determined. We then determined whether the intensity and/or duration of contact hypersensitivity in different strains of mice was influenced by the density of Thy-1+ dendritic epidermal cells or the ratio of I-A+ Langerhans cells to Thy-1+ dendritic epidermal cells. We found that there was marked variability in the density of Thy-1+ dendritic epidermal cells and I-A+ Langerhans cells in the ten strains of mice studied. The ratio of I-A+ Langerhans cells to Thy-1+ dendritic epidermal cells ranged from 0.5 in C57BL/10J mice to greater than 22 in A/J and BALB/cByJ mice. When small amounts of contact sensitizers were used to induce contact hypersensitivity (e.g., 20 micrograms of oxazolone or trinitrochlorobenzene), there was consistent strain variability in the intensity of ear swelling. There was a significant correlation between the ratio of I-A+ Langerhans cells to Thy-1+ dendritic epidermal cells and the intensity of contact hypersensitivity (Pearson's correlation coefficient 0.85, p = 0.002). Strains with the highest ratios of I-A+ Langerhans cells to Thy-1+ dendritic epidermal cells had the most ear swelling. There were no consistent differences in the duration of contact hypersensitivity observed among the ten different strains. Our results indicate that Thy-1+ dendritic epidermal cells may play a physiologic role in down-regulating contact hypersensitivity in vivo.