HLA-A2 restricted, melanocyte-specific CD8(+) T lymphocytes detected in vitiligo patients are related to disease activity and are predominantly directed against MelanA/MART1

Vitiligo is a skin and hair disorder characterized by circumscribed depigme nted lesions due to lack of melanocytes in the respective areas. It has bee n suggested that vitiligo is caused by an autoimmune-mediated destruction o f melanocytes. Recently, the presence of a high frequency of skin-homing me lanocyte-specific cytotoxic T lymphocytes in the peripheral blood of patien ts with vitiligo was reported. Our study examines the frequency of melanocy te-specific cytotoxic T lymphocytes in vitiligo patients and its relationsh ip to disease activity. Thirty-two patients with moderate to active vitilig o and 17 control subjects were included. Melanocyte specific reactive CD8() T cells were identified by enzyme-linked immunospot assay after stimulati on with five peptides from gp100, four peptides from MelanA/MART1, and two peptides from tyrosinase, In selected patients, intracellular interferon-ga mma staining for the detection of specific reactive CD8+ T cells was additi onally performed. In seven of 10 patients (70%) with actively progressive d isease CD8(+) T cells directed against melanocyte epitopes were detected, w hereas only in four of 22 patients (18%) with moderate disease activity suc h specific reactivity was found. MelanA/MART1 peptides were immunodominant in nine patients reacting against EAAGIGILTV and three patients reacting ag ainst ILTVILGVL. Intracellular interferon-gamma staining confirmed the find ings obtained by the enzyme-linked immunospot technique. The present study supports the hypothesis that vitiligo is a cytotoxic T lymphocyte-mediated autoimmune disease. The presence of melanocyte-specific reactive CD8(+) T c ells seems to be closely related to disease activity.