Regular Article

Journal of Investigative Dermatology (2001) 117, 326–332; doi:10.1046/j.1523-1747.2001.01408.x

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

Belinda Palermo*, Rita Campanelli*, Silvia Garbelli*, Stefania Mantovani*, Erica Lantelme*, Valeria Brazzelli, Marco Ardigó, Giovanni Borroni, Miriam Martinetti, Carla Badulli, Antje Necker§ and Claudia Giachino*,

  1. *Experimental Immunology, IRCCS Maugeri Foundation, Pavia, Italy
  2. Department of Human and Hereditary Pathology, Institute of Dermatology, University of Pavia, Pavia, Italy
  3. Immunohematology and Transfusion Center, IRCCS Policlinico S. Matteo, Pavia, Italy
  4. §Immunotech, a Beckman-Coulter company, Marseille, France
  5. Department of Clinical and Biological Sciences, University of Turin, Italy

Correspondence: Dr Claudia Giachino, Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, Italy. Email: cgiachino@fsm.it

Received 21 August 2000; Revised 1 March 2001; Accepted 30 March 2001.

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Abstract

Vitiligo is a common skin disease characterized by the presence of well circumscribed, depigmented, milky white macules devoid of identifiable melanocytes. Although the detection of circulating anti-melanocytic antibodies and of infiltrating lymphocytes at the margin of lesions supports the view that vitiligo is an autoimmune disorder, its etiology remains unknown. In particular, 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 melanocyte differentiation antigens Melan-A/MART1, tyrosinase, and gp100 in vitiligo patients have been investigated by the use of major histocompatibility complex/peptide tetramers. High frequencies of circulating melanocyte-specific CD8+ T cells were found in all vitiligo patients analyzed. These cells exerted anti-melanocytic cytotoxic activity in vitro and expressed skin-homing capacity. In one patient melanocyte-specific cells were characterized by an exceptionally high avidity for their peptide/major histocompatibility complex ligand. These findings strongly suggest a role for cellular immunity in the pathogenesis of vitiligo and impact on the common mechanisms of self tolerance.

Keywords:

cytotoxic T lymphocytes, human, melanocyte differentiation antigen, vitiligo

Abbreviations:

CLA, cutaneous lymphocyte-associated antigen; CTL, cytotoxic T lymphocyte; PBMC, peripheral blood mononuclear cells

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