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Diphenylcyclopropenone treatment of alopecia areata induces apoptosis of perifollicular lymphocytes
European Journal of Dermatology. Volume 16, Number 5, 537-42, September-October 2006, Investigative report
Free Article
Author(s) : Verena Herbst, Margot Zöller, Sabine Kissling, Elke Wenzel, Nathalie Stutz, Pia Freyschmidt-Paul
Summary : Alopecia areata (AA) is a T cell-mediated autoimmune disease that can be treated with the contact sensitizer diphenylcyclopropenone (DCP). Peripheral blood leukocytes from AA patients are relatively resistant to apoptosis which might be due to decreased Fas Ligand (FasL) expression, or to an increase in CD44v7 expression. Moreover it has been suggested in a murine model of AA that contact allergen treatment might interfere with the emigration of Langerhans cells into the draining lymph node, thus hampering autoreactive T-cell activation. To assess whether and which of these mechanisms is of clinical relevance, immunohistochemistry was performed in scalp biopsies of successfully DCP-treated AA patients in the early phase of hair regrowth. In line with recent studies in a murine model of AA, there was no evidence that DCP treatment would interfere with extravasation and skin homing of activated leukocytes. Perifollicular infiltrates of DCP-treated as compared to untreated AA patients actually showed an increased number of perifollicular CD8 ⁺ and CD1a ⁺ cells. Furthermore, the expression of CD44 and CD49d, which are of major importance in leukocyte extravasation, was even increased in DCP-treated as compared to AA patient infiltrates. The same accounted for the skin homing receptor CD44v10. When we evaluated the leukocyte subpopulations in DCP-treated as compared to untreated AA patients’ skin biopsies, there was an undue increase in CD1a ⁺ cells, that could well be indicative of hampering of the emigration of antigen presenting cells (APC) by allergen treatment. Most importantly, the number of perifollicular TUNEL- and FasL-positive cells was strikingly increased, whereas the number of CD44v7 ⁺ cells remained unaltered. Taken together, this study provides strong evidence that long term treatment with a contact sensitizer allows for the recovery of hair follicle by driving autoreactive T cells into activation-induced cell death. In addition the replacement with newly activated autoreactive T-cells might be impaired due to a DCP-mediated hindrance of APC emigration.
Keywords : AA, alopecia areata, APC, antigen presenting cell, DCP, diphenylcyclopropenone, FasL, FasLigand

Diphenylcyclopropenone treatment of alopecia areata induces apoptosis of perifollicular lymphocytes