Differential effects of cyclosporine A on Langerhans cells and regulatory T-cell populations in severe psoriasis: an immunohistochemical and flow cytometric analysis.
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.
Horrocks
C
C
Department of Pathology, University of Aberdeen, Scotland, UK.
Duncan
J I
JI
Sewell
H F
HF
Ormerod
A D
AD
Thomson
A W
AW
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000276:immunology; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003524:Cyclosporins / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007801:Langerhans Cells / Q000187:drug effects*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D003524:Cyclosporins