SUMMARY: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 ϩ and CD8 ϩ TCC confirmed polarization toward Type-1-like in both CD4 and CD8 compartments, which paralleled depigmentation process observed locally in the skin. Furthermore, CD8 ϩ TCC derived from two patients also were analyzed for reactivity against autologous melanocytes. The antimelanocyte cytotoxic reactivity was observed among CD8 ϩ 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. (Lab Invest 2003, 83:683-695).

Vitiligo is an acquired melanin pigmentary disorder manifesting itself by expanding depigmented lesions of the skin. To date, the etiopathomechanism of vitiligo has not been convincingly elucidated and a number of seemingly mutually opposed hypotheses with equal likelihood still coexist. Concurrent theories on vitiligo etiology, together with supportive evidence, are reviewed here. Due to the observed variation in clinical manifestations of the disease, it seems likely that the etiology of vitiligo may differ among patients. Therefore several theories on vitiligo etiopathogenesis have been combined to formulate a convergence theory for vitiligo, also presented in this article. This theory states that stress, accumulation of toxic compounds, infection, autoimmunity, mutations, altered cellular environment and impaired melanocyte migration and/or proliferation can all contribute to vitiligo etiopathogenesis in varying proportions.

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We report the detailed electronic structure of WTe2 by high resolution angle-resolved photoemission spectroscopy. We resolved a rather complicated Fermi surface of WTe2. Specifically, there are in total nine Fermi pockets, including one hole pocket at the Brillouin zone center Γ, and two hole pockets and two electron pockets on each side of Γ along the Γ-X direction. Remarkably, we have observed circular dichroism in our photoemission spectra, which suggests that the orbital angular momentum exhibits a rich texture at various sections of the Fermi surface. This is further confirmed by our density-functional-theory calculations, where the spin texture is qualitatively reproduced as the conjugate consequence of spin-orbital coupling. Since the spin texture would forbid backscatterings that are directly involved in the resistivity, our data suggest that the spin-orbit coupling and the related spin and orbital angular momentum textures may play an important role in the anomalously large magnetoresistance of WTe2. Furthermore, the large differences among spin textures calculated for magnetic fields along the in-plane and out-of-plane directions also provide a natural explanation of the large field-direction dependence on the magnetoresistance.