Autoimmune Destruction of Skin Melanocytes by Perilesional T Cells from Vitiligo Patients

In vitiligo, cytotoxic T cells infiltrating the perilesional margin are suspected to be involved in the pathogenesis of the disease. However, it remains to be elucidated whether these T cells are a cause or a consequence of the depigmentation process. T cells we obtained from perilesional skin biops...

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Bibliographic Details
Published in:	Journal of investigative dermatology 2009-09, Vol.129 (9), p.2220-2232
Main Authors:	van den Boorn, Jasper G., Konijnenberg, Debby, Dellemijn, Trees A.M., Wietze van der Veen, J.P., Bos, Jan D., Melief, Cornelis J.M., Vyth-Dreese, Florry A., Luiten, Rosalie M.
Format:	Article
Language:	eng
Subjects:	Apoptosis Autoimmunity Biological and medical sciences Cytotoxicity, Immunologic Dermatology Humans Interleukin-17 - physiology Lymphocyte Activation Medical sciences Melanocytes - immunology Melanocytes - pathology Pigmentary diseases of the skin Skin - immunology Skin - pathology T-Lymphocytes - immunology Vitiligo - etiology Vitiligo - immunology Vitiligo - pathology
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Summary:	In vitiligo, cytotoxic T cells infiltrating the perilesional margin are suspected to be involved in the pathogenesis of the disease. However, it remains to be elucidated whether these T cells are a cause or a consequence of the depigmentation process. T cells we obtained from perilesional skin biopsies, were significantly enriched for melanocyte antigen recognition, compared with healthy skin-infiltrating T cells, and were reactive to melanocyte antigen-specific stimulation. Using a skin explant model, we were able to dissect the in situ activities of perilesional T cells in the effector phase of depigmentation. We show that these T cells could infiltrate autologous normally pigmented skin explants and efficiently kill melanocytes within this microenvironment. Interestingly, melanocyte apoptosis was accompanied by suprabasal keratinocyte apoptosis. Perilesional T cells did, however, not induce apoptosis in lesional skin, which is devoid of melanocytes, indicating the melanocyte-specific cytotoxic activity of these cells. Melanocyte killing correlated to local infiltration of perilesional T cells. Our data show that perilesional cytotoxic T cells eradicate pigment cells, the characteristic hallmark of vitiligo, thereby providing evidence of T cells being able to mediate targeted autoimmune tissue destruction.
ISSN:	0022-202X 1523-1747