Melanocyte-specific CD8+ T cells are associated with epidermal depigmentation in a novel mouse model of vitiligo

作者: S. You , Y.-H. Cho , J.-S. Byun , E.-C. Shin

DOI: 10.1111/CEI.12146

关键词: MelanocyteDegranulationAntigenDepigmentationCytotoxic T cellCD8BiologyImmunologyDermisVitiligo

摘要: In the present study, we established a novel murine model of vitiligo by sequential prime/boost immunizations into hind footpad and tail dermis with tyrosinase-related protein 2 (TRP2)-180 (SVYDFFVWL) peptide, lipopolysaccharides cytosine-phosphate-guanosine (CpG) oligodeoxynucleotides. Immunized mice developed epidermal depigmentation in skin without hair depigmentation, thereby differentiating this approach from models vitiligo. Following intradermal immunization, activated CD8(+) interferon (IFN)-γ(+) T cells were recruited locally to skin. In-vivo cytotoxicity assays demonstrated specific lysis TRP2-180-presenting immunized mice. Furthermore, extent correlated frequency TRP2-180-specific splenic cells, as determined IFN-γ tumour necrosis factor (TNF)-α production, cytotoxic degranulation evidenced CD107a staining. These findings suggest correlation between presence effector development depigmented lesions our model. This new vitiligo, characterized is more similar human disease than previous models. Therefore, well suited future studies on pathogenesis therapeutics for

参考文章(16)
Randal K. Gregg, Lisa Nichols, Yiming Chen, Bao Lu, Victor H. Engelhard, Mechanisms of spatial and temporal development of autoimmune vitiligo in tyrosinase-specific TCR transgenic mice. Journal of Immunology. ,vol. 184, pp. 1909- 1917 ,(2010) , 10.4049/JIMMUNOL.0902778
Jian Cui, Li-Yu Shen, Guang-chao Wang, Role of hair follicles in the repigmentation of vitiligo. Journal of Investigative Dermatology. ,vol. 97, pp. 410- 416 ,(1991) , 10.1111/1523-1747.EP12480997
Frédérique-Anne Le Gal, Philippe Lefebvre, Jean-Christophe Deschemin, Muriel Andrieu, Jean-Gérard Guillet, Marie-Françoise Avril, Jacques Bosq, Martin-Xavier Dore, Direct evidence to support the role of antigen-specific CD8(+) T cells in melanoma-associated vitiligo. Journal of Investigative Dermatology. ,vol. 117, pp. 1464- 1470 ,(2001) , 10.1046/J.0022-202X.2001.01605.X
Rochelle L Mandelcorn-Monson, Neil H Shear, Eddy Yau, Suryaprakash Sambhara, Brian H Barber, David Spaner, Mark A DeBenedette, None, Cytotoxic T lymphocyte reactivity to gp100, MelanA/MART-1, and tyrosinase, in HLA-A2-positive vitiligo patients. Journal of Investigative Dermatology. ,vol. 121, pp. 550- 556 ,(2003) , 10.1046/J.1523-1747.2003.12413.X
Belinda Palermo, Rita Campanelli, Silvia Garbelli, Stefania Mantovani, Erica Lantelme, Valeria Brazzelli, Marco Ardigó, Giovanni Borroni, Miriam Martinetti, Carla Badulli, Antje Necker, Claudia Giachino, None, 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 Journal of Investigative Dermatology. ,vol. 117, pp. 326- 332 ,(2001) , 10.1046/J.1523-1747.2001.01408.X
Ali Alikhan, Lesley M. Felsten, Meaghan Daly, Vesna Petronic-Rosic, Vitiligo: A comprehensive overview: Part I. Introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up Journal of The American Academy of Dermatology. ,vol. 65, pp. 473- 491 ,(2011) , 10.1016/J.JAAD.2010.11.061
Karl Sebastian Lang, Alexandra Muhm, Arnaud Moris, Stefan Stevanovic, Hans-Georg Rammensee, Constanze Charlotte Caroli, Dorothee Wernet, Birgit Schittek, Evelyn Knauss-Scherwitz, Claus Garbe, HLA-A2 Restricted, Melanocyte-Specific CD8+ T Lymphocytes Detected in Vitiligo Patients are Related to Disease Activity and are Predominantly Directed Against MelanA/MART1 Journal of Investigative Dermatology. ,vol. 116, pp. 891- 897 ,(2001) , 10.1046/J.1523-1747.2001.01363.X
Gun Yoen Na, Seon Kyo Seo, Sung Kwan Choi, Single hair grafting for the treatment of vitiligo Journal of The American Academy of Dermatology. ,vol. 38, pp. 580- 584 ,(1998) , 10.1016/S0190-9622(98)70121-5
Jasper G. van den Boorn, Debby Konijnenberg, Trees A.M. Dellemijn, J.P. Wietze van der Veen, Jan D. Bos, Cornelis J.M. Melief, Florry A. Vyth-Dreese, Rosalie M. Luiten, Autoimmune destruction of skin melanocytes by perilesional T cells from vitiligo patients. Journal of Investigative Dermatology. ,vol. 129, pp. 2220- 2232 ,(2009) , 10.1038/JID.2009.32