1. ¹Department of Pathology, Academic Medical Center/University of Amsterdam, The Netherlands
2. ²Department of Dermatology, Academic Medical Center/University of Amsterdam, The Netherlands
3. ³Dutch Institute for Pigmentary Disorders (SNIP), Amsterdam, The Netherlands
4. ⁴MRC Human Immunology Unit, Institute of Molecular Medicine, Oxford, United Kingdom
5. ⁵University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania

Correspondence: Dr. P.K. Das, Department of Pathology (L2-258), Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. E-mail: p.k.das@amc.uva.nl

Received 26 September 2002.

Abstract

Vitiligo is an autoimmune condition characterized by loss of epidermal melanocytes. High frequencies of melanocyte-reactive cytotoxic T cells in the peripheral blood of vitiligo patients and the observed correlation between perilesional T-cell infiltration and melanocyte loss in situ suggest the important role of cellular autoimmunity in the pathogenesis of this disease. We isolated T cells from both perilesional and nonlesional skin biopsies obtained from five vitiligo patients, then cloned and analyzed their profile of cytokine production after short-term, nonspecific expansion in vitro. Perilesional T-cell clones (TCC) derived from patients with vitiligo exhibited a predominant Type-1–like cytokine secretion profile, whereas the degree of Type-1 polarization in uninvolved skin-derived TCC correlated with the process of microscopically observed melanocyte destruction in situ. Detailed analysis of broad spectrum of cytokines produced by perilesional- and nonlesional-derived CD4⁺ and CD8⁺ TCC confirmed polarization toward Type-1–like in both CD4 and CD8 compartments, which paralleled depigmentation process observed locally in the skin. Furthermore, CD8⁺ TCC derived from two patients also were analyzed for reactivity against autologous melanocytes. The antimelanocyte cytotoxic reactivity was observed among CD8⁺ TCC isolated from perilesional biopsies of two patients with vitiligo. Finally, in two of five patients, tetramer analysis revealed presence of high frequencies of Mart-1–specific CD8 T cells in T-cell lines derived from perilesional skin. Altogether our data support the role of cellular mechanisms playing a significant part in the destruction of melanocytes in human autoimmune vitiligo.