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*,¶
- *Experimental Immunology, IRCCS Maugeri Foundation, Pavia, Italy
- †Department of Human and Hereditary Pathology, Institute of Dermatology, University of Pavia, Pavia, Italy
- ‡Immunohematology and Transfusion Center, IRCCS Policlinico S. Matteo, Pavia, Italy
- §Immunotech, a Beckman-Coulter company, Marseille, France
- ¶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.
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



