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 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.
van den Boorn
Jasper G
JG
Department of Dermatology, Netherlands Institute for Pigment Disorders, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Konijnenberg
Debby
D
Dellemijn
Trees A M
TA
van der Veen
J P Wietze
JP
Bos
Jan D
JD
Melief
Cornelis J M
CJ
Vyth-Dreese
Florry A
FA
Luiten
Rosalie M
RM
D017209:Apoptosis; D015551:Autoimmunity; D003602:Cytotoxicity, Immunologic; D006801:Humans; D020381:Interleukin-17 / Q000502:physiology; D008213:Lymphocyte Activation; D008544:Melanocytes / Q000276:immunology / Q000473:pathology*; D012867:Skin / Q000276:immunology / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology; D014820:Vitiligo / Q000209:etiology / Q000276:immunology* / Q000473:pathology
D020381:Interleukin-17