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

Abstract

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

• Authors: S You, Y-H Cho, J-S Byun, E-C Shin
• Journal: Clinical and experimental immunology (Clin Exp Immunol) Vol. 174 Issue 1 Pg. 38-44 (Oct 2013) ISSN: 1365-2249 [Electronic] England
• PMID: 23711243 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 British Society for Immunology.

Chemical References

• Membrane Proteins
• Peptide Fragments
• peptide SVYDFFVWL

Topics

• Animals
• CD8-Positive T-Lymphocytes (immunology, metabolism, pathology)
• Disease Models, Animal
• Epidermis (immunology, metabolism, pathology)
• Humans
• Male
• Melanocytes (immunology, pathology)
• Membrane Proteins (administration & dosage, immunology)
• Mice
• Mice, Inbred C57BL
• Peptide Fragments (administration & dosage, immunology)
• Pigmentation Disorders (etiology, immunology, pathology)
• Vaccination (methods)
• Vitiligo (etiology, immunology, metabolism, pathology)