Comparative immunophenotypic study of lichen sclerosus - Epidermotropic CD57+lymphocytes are numerous - Implications for pathogenesis

To characterize the immunophenotype of inflammatory cells in lichen scleros us (LS), we performed a comparative case control study using one- and two-c olor immunohistochemistry and the nitro blue tetrazolium (NBT) reaction. St udy material consisted of 100 biopsies from patients with LS or from 12 con trol groups consisting of inflammatory, scarring, and depigmenting cutaneou s disorders. In addition, fresh tissue was sampled from four vulvectomy spe cimens for NET testing. The typical inflammatory infiltrate of LS contained numerous epidermotropic CD3+, CD8+, CD57+ cells, increased intraepidermal HLA-DR+ cells, and a dermal infiltrate rich in CD8+, CD57+, HLA-DR+, and CD 68+ inflammatory cells. Comparing LS to the 12 control groups, epidermotrop ic CD57+ lymphocytes independently predicted LS (P = 0.006, logistic regres sion, multivariate analysis). Among the 12 control groups, only specimens o f the inflammatory stage of morphea exhibited numerous dermal CD57+ lymphoc ytes. Two-color immunohistochemistry confirmed the CD3+/CD8+CD57+ and CD3+/ CD8+/CD57+HLA-DR-+ epidermotropic and dermal lymphocytic phenotypes and the dermal macrophage CD68+HLA-DR+ phenotype. In LS, the NET reaction revealed evidence of superoxide production associated with CD68+HLA-DR+ cells. Expa nsion of CD8+CD57+ lymphocytes is associated with viral infections, autoimm une disease, malignancies, and transplantation and is suspected to be the r esult of chronic excessive antigen challenge. In these pathologic states, C D8+CD57+ lymphocytes (as terminally differentiated, antigen-specific T cell s) participate in the suppression of cytolytic activity to limit tissue dam age. In LS, activated macrophages and lymphocytes indicate persistent antig en-driven inflammation. LS's numerous CD8+CD57+ lymphocytes may be either t he mediators or the consequence of its hallmark sclerosis.