Immunological aspects of oral lichen planus. Studies on the expression of cytokines, T cell receptor V-families and delayed-type hypersensitivity reactions

Abstract

Oral lichen planus (OLP) is a chronic inflammatory disease of unknown etiology. In lesions, T lymphocytes constitute the major infiltrating cell type. The present series of studies focussed on studying phenotypic, distributional and functional aspects of T cells in lesions and in blood in OLP patients, by virtue of the central role of these cells in mediating inflammatory reactions. The expression of T cell receptor V-families was assessed in biopsies. The frequency and distribution of mRNA positive cells for IFN-g, IL-2, IL-4, IL-10, TNF-a and TGF-b were assessed in OLP infiltrates, in situ. The number of IFN-g producing cells and the level of secretion of this cytokine was determined in blood mononuclear cells, from patients and from matched controls. Finally, the in vivo capacity of T lymphocytes to elicit delayed-type hypersensitivity reactions in skin was compared in OLP and in matched controls.Of the eleven T cell receptor V-families investigated, the Vb3 and the Va2 families were represented on approximately 24 % of the infiltrating cells in OLP. By contrast, in control sections from C. albicans infiltrates, the two V-families were found in only 0-7 % of the total number of infiltrating cells, corresponding with levels detected for each V-family in healthy blood donors. The remaining V-families were each expressed in low frequency. The restricted V-family expression in OLP lesions was interpreted as potentially being initiated by superantigens.The number of cytokine mRNA producing cells in lesions was estimated to 1 % (IFN-g) or range between 1-2 % (IL-2, IL-4, IL-10, TNF-a and TGF-b), respectively. The mRNA positive cells were distributed in association with the basement membrane, in a majority of the biopsies, suggesting that interaction with antigen-presenting cells occurs in this region. The low frequency of cytokine mRNA positive cells also suggests that the disease is maintained by few antigen-specific T lymphocytes.Similar numbers of IFN-g producing cells in blood was found in patients and controls, in response to mitogen (phytohaemagglutinin), Candida albicans antigen or when cells were left unstimulated. The levels of IFN-g that were secreted in supernatants were equivalent in patients and matched controls, for the respective antigens. Delayed-type hypersensitivity responses to the recall antigens mumps, tuberculin and streptokinase/streptodornase were reduced in oral lichen planus patients compared with matched controls. By contrast, the reponse to C. albicans was similar in patients and controls. This finding suggests that memory T cell responses to infrequently encountered antigens, represented by mumps, tuberculin and streptokinase/streptodornase may be qualitatively and/or quantitatively reduced in OLP. Memory responses to frequently recognized antigens or antigens that are part of the ubiquitous flora, such as C. albicans, may instead remain unaltered.