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.
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.
Palermo
B
B
Experimental Immunology, IRCCS Maugeri Foundation, Pavia, Italy.
Campanelli
R
R
Garbelli
S
S
Mantovani
S
S
Lantelme
E
E
Brazzelli
V
V
Ardigó
M
M
Borroni
G
G
Martinetti
M
M
Badulli
C
C
Necker
A
A
Giachino
C
C
D000951:Antigens, Neoplasm; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D005260:Female; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D058965:MART-1 Antigen; D008297:Male; D008544:Melanocytes / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000494:pharmacology*; D014442:Monophenol Monooxygenase / Q000276:immunology / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000276:immunology / Q000494:pharmacology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D014820:Vitiligo / Q000276:immunology* / Q000473:pathology; D058951:gp100 Melanoma Antigen
D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; D058965:MART-1 Antigen; C548667:MLANA protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D010446:Peptide Fragments; D058951:gp100 Melanoma Antigen; D014442:Monophenol Monooxygenase