Lack of functionally active Melan-A(26-35)-specific T cells in the blood of HLA-A2+ vitiligo patients.
Vitiligo, a skin disorder characterized by the spontaneous destruction of melanocytes, is believed to be of autoimmune origin. We investigated the presence and functionality of CD8(+) T-cells specific for the melanocyte-associated antigens Melan-A, gp100, tyrosinase, and TRP-2 in the blood of HLA-A2(+) vitiligo patients. We enumerated antigen-specific CD8(+) T cells by major histocompatibility complex multimer staining directly ex vivo, as well as after 9 days of in vitro stimulation and assessed IFN-gamma secretion by enzyme-linked immunospot (Elispot) assay. Tyrosinase-, gp100-, or TRP-2-specific CD8(+) T cells could not be identified in the peripheral blood of individuals with vitiligo. Although Melan-A-specific T cells were detectable at levels comparable to Flu-MP-specific T cells by multimer staining, these lymphocytes did not express the skin-homing receptor cutaneous lymphocyte antigen, were phenotypically naïve (CD45RA(+)), and were unresponsive in the IFN-gamma Elispot assay, suggesting that they are unlikely to be involved in the etiopathogenesis of vitiligo.
Adams
Sylvia
S
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY, USA. sylvia.adams@med.nyu.edu
Lowes
Michelle A
MA
O'Neill
David W
DW
Schachterle
Stephen
S
Romero
Pedro
P
Bhardwaj
Nina
N
D000951:Antigens, Neoplasm / Q000097:blood / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D015789:HLA-A2 Antigen / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D058965:MART-1 Antigen; D008562:Membrane Glycoproteins / Q000097:blood / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009363:Neoplasm Proteins / Q000097:blood / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D014820:Vitiligo / Q000097:blood* / Q000209:etiology / Q000473:pathology; D058951:gp100 Melanoma Antigen
D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; D058965:MART-1 Antigen; C548667:MLANA protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D010446:Peptide Fragments; D058951:gp100 Melanoma Antigen; C500290:peptide SVYDFFVWL; D007371:Interferon-gamma; D014442:Monophenol Monooxygenase