The effects of cyclosporin A on T lymphocyte and dendritic cell sub-populations in psoriasis

Abstract

Sequential skin biopsies from six patients with severe psoriasis were studied during treatment with cyclosporin. Four of the patients cleared completely and the remaining two showed a marked improvement. A subset of dendritic cells, HLA-DR+ but lacking the T6 antigen characteristically expressed by Langerhans cells (DR+ 6-), was observed in lesional epidermis. They disappeared during treatment, before clinical improvement was apparent and at a rate which correlated with clearance of psoriasis. These cells were not found in normal or uninvolved psoriatic epidermis and their number in lesional skin appeared to be related to the clinical severity of the disease. Total numbers of CD4 and CD8, and HLA-DR+ CD8 T cells were substantially reduced in both epidermis and dermis prior to clinical improvement. In contrast, there was generally no decrease in the number of HLA-DR+ CD4 T cells in the epidermis during resolution, whereas these cells were reduced by an average of 68% in the dermis. The beneficial effects of cyclosporin in psoriasis further support the hypothesis that T cells play a central role in the pathogenesis of psoriasis. The cellular changes observed in the skin during cyclosporin treatment may help to elucidate the effects of this drug on immunoregulatory mechanisms in man.

Resolution of psoriasis following allogeneic bone marrow transplantation for chronic myelogenous leukemia: Case report and review of the literature

“…This is supported by the observation that CsA improves psoriasis, suggesting that its effect may be mediated by anti-T cell activity [12]. It has been also reported that psoriasis is exacerbated by interferon-␣, which may activate autoreactive T cells [13].…”

CD69, HLA-DR and the IL-2R Identify Persistently Activated T Cells in Psoriasis Vulgaris Lesional Skin: Blood and Skin Comparisons by Flow Cytometry

“…In addition, several investigators have shown that immunosuppressive treatment induces clearance of infiltrating T cells prior to clinical improvement [9,13].…”

“…Recovering (thinning) skin has fewer T cells, most markedly in the epidermis [4]. Indirect evidence for T cell mediation is shown in therapies which affect activated T cells such as PUVA [5], UVB broad and narrow band [6,7], cyclosporin A [8,9] and FK 506 [10][11][12] whose success also correlates with the loss of epidermal T cells.…”

The Immunologic and Genetic Basis of Psoriasis

“…[16][17][18][19][20] Likewise, when psoriatic plaques were examined after administration of various treatments, the resolving lesions were characterized by prominent reductions in CD4 + and/or CD8 + T cells from the epidermis. [9][10][11][21][22][23] In contrast to these divergent observations, there is more of a consensus that cytokine production by activated T cells resembles a T-helper type-1 profile with interferon gamma (IFN-␥) and interleukin (IL) 12, but not IL-4, IL-5, or IL-10. 24,25 To resolve the dilemma regarding relative roles for CD4 + and CD8 + T cells, engrafted PN skin was separately injected with highly purified CD4 + or CD8 + T-cell lines.…”