HIGH-FREQUENCY OF SKIN-HOMING MELANOCYTE-SPECIFIC CYTOTOXIC T-LYMPHOCYTES IN AUTOIMMUNE VITILIGO

Vitiligo is an autoimmune condition characterized by loss of epidermal melanocytes. Using tetrameric complexes of human histocompatibility l eukocyte antigen (HLA) class I to identify antigen-specific T cells ex vivo, we observed high frequencies of circulating MelanA-specific, A 0201-restricted cytotoxic T lymphocytes (A2-MelanA tetramer(+) CTLs) i n seven of nine HLA-A0201-positive individuals with vitiligo. Isolate d A2-MelanA tetramer(+) CTLs were able to lyse A0201-matched melanoma cells in vitro and their frequency ex vivo correlated with extent of disease. In contrast, no A2-MelanA tetramer(+) CTL could be identified ex vivo in all four A0201-negative vitiligo patients or five of six A0201-positive asymptomatic controls. Finally, we observed that the A 2-MelanA tetramer(+) CTLs isolated from vitiligo patients expressed hi gh levels of the skin homing receptor, cutaneous lymphocyte-associated antigen, which was absent from the CTLs seen in the single A0201-pos itive normal control. These data are consistent with a role of skin-ho ming autoreactive melanocyte-specific CTLs in causing the destruction of melanocytes seen in autoimmune vitiligo. Lack of homing receptors o n the surface of autoreactive CTLs could be a mechanism to control per ipheral tolerance in vivo.