Specific cytotoxic T lymphocyte responses against Melan-A/MART1, tyrosinase and Gp100 in vitiligo by the use of major histocompatibility complex/peptide tetramers: the role of cellular immunity in the etiopathogenesis of vitiligo

Vitiligo is a common skin disease characterized by the presence of well cir cumscribed, depigmented, milky white macules devoid of identifiable melanoc ytes. Although the detection of circulating anti-melanocytic antibodies and of infiltrating lymphocytes at the margin of lesions supports the view tha t vitiligo is an autoimmune disorder, its etiology remains unknown. In part icular, it is still a matter of debate whether the primary pathogenic role is exerted by humoral or cellular abnormal immune responses. In this study, the presence of specific cytotoxic T lymphocyte responses against the mela nocyte differentiation antigens Melan-A/MART1, tyrosinase, and gp100 in vit iligo patients have been investigated by the use of major histocompatibilit y complex/peptide tetramers. High frequencies of circulating melanocyte-spe cific CD8(+) T cells were found in all vitiligo patients analyzed. These ce lls exerted anti-melanocytic cytotoxic activity in vitro and expressed skin -homing capacity. In one patient melanocyte-specific cells were characteriz ed by an exceptionally high avidity for their peptide/major histocompatibil ity complex ligand. These findings strongly suggest a role for cellular imm unity in the pathogenesis of vitiligo and impact on the common mechanisms o f self tolerance.