Differential effects of cyclosporine A on Langerhans cells and regulatory T-cell populations in severe psoriasis: an immunohistochemical and flow cytometric analysis |
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Authors: | C Horrocks J I Duncan H F Sewell A D Ormerod A W Thomson |
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Affiliation: | Department of Pathology, University of Aberdeen, Scotland, UK. |
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Abstract: | Systemic administration of cyclosporine A (Cy-A; initial dose 5 or 2.5 mg/kg/day) to patients with severe chronic plaque psoriasis produced marked reductions in psoriasis area and severity index within 4 weeks. The clinical response was accompanied, within 1 week, by progressive reductions in T-cell subpopulations (CD3+ and CD4+) and in numbers of interleukin-2 receptor (IL-2-R)-positive (CD25+) cells within lesional skin. Over the first 4 weeks of treatment, these changes were accompanied by reductions in DR+ cells within the epidermis (minor) and dermis (substantial). In contrast, numbers of epidermal CD1+ cells increased substantially during resolution of the skin lesions. Unlike lesional skin, however, no significant changes in absolute numbers of circulating immunoregulatory T-cell populations, including helper/inducer (CD45R) and suppressor/inducer (CD29W) subsets, quantified by dual immunofluorescence labelling, were detected. Moreover, numbers of blood-borne HLA-DR, IL-2-R and transferrin receptor (CD71) positive lymphocytes were unaffected by Cy-A therapy, nor were any differences detected between psoriatic patients and normal controls using these cell markers. Our data suggest that the immunoregulatory effects of Cy-A in psoriasis are mediated via lesional T lymphocytes and that epidermal CD1+ DR- dendritic cells may play an influential role in the regulation of T-cell function and keratinocyte growth during resolution of the skin lesions. |
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