Stephen I. Katz

Abstract Langerhans cells (LC) constitute a morphologically well-characterized minor subpopulation of the mammalian epidermis whose functional role is still a matter of conjecture. The hypothesis that LC represent an epidermal equivalent to cells of the monocyte-macrophage-histiocyte series is supported by the recent observations that in humans and guinea pigs LC are the only epidermal cells that express Fc-IgG receptors, C3 receptors, and Ia antigens. Using inbred strain 2 and strain 13 guinea pigs, we investigated in this study whether LC can mediate the same immunologic functions as Ia-bearing macrophages. LC-enriched and LC-depleted epidermal cells were prepared by separation of Fc-IgG rosetting epidermal cells on density gradients. When both populations were tested for the biosynthesis of alloantigens by immunoprecipitation techniques, Ia antigen synthesis was restricted to the LC-enriched fraction. Functional studies demonstrated that antigen-pulsed LC-enriched epidermal cells induce a proliferative response in immune T cells that is comparable in magnitude to that seen with macrophages. Moreover, effective presentation of immunologically relevant antigen requires syngeneity between LC-enriched epidermal cells and responder lymphocytes. In the mixed leukocyte reaction (MLR), LC-enriched epidermal cells were as effective stimulators as macrophages. LC-depleted epidermal cells, by contrast, induced little or no stimulation in both assay systems. Both the antigen-presenting and the MLR-stimulatory capacities of LC-enriched epidermal cells could be abrogated by pretreatment with anti-Ia sera and complement. The presence in the epidermis of Ia-bearing LC, capable of mediating the immunologic functions of Ia-bearing macrophages, has important clinical implications with regard to the role of LC as sensitizing cells in both contact hypersensitivity and skin graft rejection.

Relapsing polychondritis is a disorder of unknown cause characterized by the destruction of cartilage. To test the hypothesis that immunologic mechanisms are involved in the pathogenesis of relapsing polychondritis, we analyzed the serum of 15 patients for the presence of antibodies to cartilage. Antibodies to Type II (cartilage) collagen were found in the serum of five patients at the time of acute symptoms. No antibodies were detected either to cartilage proteoglycan or to other collagen types. The antibodies were detected at the onset of the disease and their titers appeared to correlate with severity of disease. Circulating immune complexes were also detected in the serum of these patients. Our findings support an immunologic involvement in this condition.