Erik R. Hansen

Calcipotriol inhibits the proliferation of hyperproliferative CD29 positive keratinocytes in psoriatic epidermis in the absence of an effect on the function and number of antigen-presenting cells.

The aim of this study was to elucidate some of the possible mechanisms of action of the vitamin D analogue calcipotriol in vivo. Calcipotriol is finding increasing use in the treatment of psoriasis, but the primary target cell in vivo has not yet been identified. We treated psoriatic patients and healthy volunteers with calcipotriol and placebo ointment for 4 and 7 days, and obtained epidermal cell suspensions from treated areas. Epidermal cells were cocultured with autologous T cells, isolated from peripheral blood, in the absence or the presence of a classical antigen or a superantigen. In both psoriatic and normal skin, calcipotriol treatment did not alter the capacity of epidermal antigen‐presenting cells to stimulate the proliferation of autologous T cells, either in the absence or in the presence of exogenous antigen. Epidermal cell suspensions were analysed further by staining for infiltrating leucocytes (CD45+) and Langerhans cells (CD1a+). Flow cytometric analyses showed that calcipotriol did not alter the number of CD45+ cells or Langerhans cells in psoriatic skin. These results indicate that calcipotriol does not alter either the number or the function of epidermal antigen‐presenting cells in psoriatic epidermis. In contrast, we found that calcipotriol significantly inhibited the proliferation of epidermal cells isolated from psoriatic skin after in vivo treatment, as determined by propidium iodide staining and flow cytometry. More specifically, we stained for CD29+ keratinocytes and found an even more significant reduction in proliferative capacity. This cell type contains the population of hyperproliferative keratinocytes in psoriatic epidermis. In conclusion, calcipotriol seems to act via an inhibitory effect on hyperproliferative basal keratinocytes of psoriatic epidermis, rather than via an effect on infiltrating leucocytes, including antigen‐presenting cells.

THE CELLULAR IMMUNE RESPONSE TO HUMAN PAPILLOMAVIRUS INFECTION

This review will concentrate on the human cellular immune response associated with the HPV infection

Lesional alopecia areata T lymphocytes downregulate epithelial cell proliferation

Alopecia areata is characterized by peribulbar infiltration by activated T cells. The function of these T cells in the pathogenesis is unknown. To elucidate the potential role of lesional T cells in the regulation of hair growth, T-cell clones from the margin of involved alopecia areata lesions from three patients were obtained by cloning, using the limiting dilution method. Of these T-cell clones, 31 were CD4+CD8–, 15 were CD8+CD4– and 2 were CD4–CD8–. The T-cell clones were activated and the supernatant harvested 24 h later and tested for its capacity to regulate proliferation of neonatal keratinocytes. The majority of the T-cell clone supernatants inhibited epithelial cell proliferation in a dose-dependent fashion. When the cytokine profiles of conditioned T-cell medium were compared with the growth-regulatory capacity, it was found that T-cell clones that released high amounts of interferon gamma and/or tumour necrosis factor alpha inhibited keratinocyte growth. In conclusion, T cells derived from the margin of active alopecia areata lesions are able to downregulate epithelial cell proliferation. This points to an important role of the immune system, especially the T cells, in this disease.

Phenotype, Ultrastructure, and Function of CD1+DR+ Epidermal Cells that Express CD36 (OKM5) in Cutaneous T‐Cell Lymphoma

This study investigated the phenotype and function of different antigen‐presenting cells (APC) present within the epidermis of patients with cutaneous T‐cell lymphoma (CTCL). Involved epidermis of CTCL compared with uninvolved was found to contain increased numbers of CDI + DR+ APC. This population was heterogeneous and comprised both leucocytes of a novel CD1+DR+CD36 (OK.M5)+ phenotype and CD1+DR+CD36− indeterminate/Langerhans cells. The CD1+DR+CD36+ leucocytes did not express TcR‐1, CD5, CD 15. or CD22, and only a minor population expressed CD11, demonslrating that they were neither T nor B cells, and did not belong lo the major CD11+ (OKM1+) blood monocyte population. Electron microscopy of purified CD36+ lesional epidermal cells (EC) demonstrated that they lacked Birbeck granules found on CD1+‐selected Langerhans cells, and most cells exhibited features of indeterminate cells or macrophages.

In cutaneous T-cell lymphoma, class II MHC molecules on CD1+ antigen-presenting cells are upregulated in involved compared with uninvolved epidermis

CD1+ antigen‐presenting cells in involved epidermis of patients with cutaneous T‐cell lymphoma exhibit an enhanced functional capacity to activate autologous CD4+ T cells compared with CD1+ antigen‐presenting cells from uninvolved and normal epidermis. Class II major histocompatibility complex molecules are involved in antigen presentation, and their expression on CD1+ Langerhans cells is known to vary. The expression of all three class II (HLA‐DR, ‐DQ, ‐DP) molecules was therefore determined on CD1+ epidermal cells from both involved and uninvolved epidermis, using flow cytometry. The involved CD1+ epidermal cells exhibited a 1.5–1.6‐fold, statistically significant increase in fluorescence intensity after staining of the class II molecules (HLA‐DR, ‐DQ, ‐DP) compared with CD1+ epidermal cells from uninvolved epidermis. The autologous CD4+ T‐cell activation was almost completely blocked by anti‐HLA‐DR, and partly by anti‐HLA‐DQ and anti‐HLA‐DP.