Interferon-gamma Inhibits Melanogenesis and Induces Apoptosis in Melanocytes: A Pivotal Role of CD8+ Cytotoxic T Lymphocytes in Vitiligo

Increased expression of the cytokine interferon (IFN)-gamma plays a pivotal role in vitiligo-induced depigmentation. However, the major source of IFN-gamma in vitiligo patients and the mechanisms underlying melanocyte destruction are unknown. In this study, a large number of skin infiltrating IFN-gamma(+) cells and CD8(+) T cells were detected in progressive vitiligo. Among the peripheral blood mononuclear cells (PBMCs) of vitiligo patients, CD8(+) cytotoxic T lymphocytes (CTLs) that express IFN-gamma exhibited significant expansion, which suggests that activated CTLs are the main source of increased IFN-gamma in progressive vitiligo. An in vitro analysis demonstrated that IFN-gamma inhibits melanogenesis in primary cultured human melanocytes by altering melanogenic enzyme mRNA expression and, more importantly, that IFN-gamma directly induces melanocyte apoptosis. Our data indicate that vitiligo pathophysiology may be linked to globally activated CD8(+) CTL subpopulations, which produce increased IFN-gamma and induce melanocyte dysfunction and apoptosis.