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

J Invest Dermatol. 2001 Jun;116(6):891-7. doi: 10.1046/j.1523-1747.2001.01363.x.

Abstract

Vitiligo is a skin and hair disorder characterized by circumscribed depigmented lesions due to lack of melanocytes in the respective areas. It has been suggested that vitiligo is caused by an autoimmune-mediated destruction of melanocytes. Recently, the presence of a high frequency of skin-homing melanocyte-specific cytotoxic T lymphocytes in the peripheral blood of patients with vitiligo was reported. Our study examines the frequency of melanocyte-specific cytotoxic T lymphocytes in vitiligo patients and its relationship to disease activity. Thirty-two patients with moderate to active vitiligo and 17 control subjects were included. Melanocyte specific reactive CD8(+) T cells were identified by enzyme-linked immunospot assay after stimulation with five peptides from gp100, four peptides from MelanA/MART1, and two peptides from tyrosinase. In selected patients, intracellular interferon-gamma staining for the detection of specific reactive CD8(+) T cells was additionally performed. In seven of 10 patients (70%) with actively progressive disease CD8(+) T cells directed against melanocyte epitopes were detected, whereas only in four of 22 patients (18%) with moderate disease activity such specific reactivity was found. MelanA/MART1 peptides were immunodominant in nine patients reacting against EAAGIGILTV and three patients reacting against ILTVILGVL. Intracellular interferon-gamma staining confirmed the findings 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 cells seems to be closely related to disease activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Differentiation, T-Lymphocyte
  • Antigens, Neoplasm
  • CD8-Positive T-Lymphocytes / immunology*
  • Female
  • HLA-A2 Antigen / immunology*
  • Humans
  • Interferon-gamma / biosynthesis
  • MART-1 Antigen
  • Male
  • Melanocytes / immunology*
  • Membrane Glycoproteins / analysis
  • Middle Aged
  • Neoplasm Proteins
  • Vitiligo / immunology*

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • Antigens, Neoplasm
  • CTAGE1 protein, human
  • HLA-A2 Antigen
  • MART-1 Antigen
  • MLANA protein, human
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • Interferon-gamma