TITLE:
Dysregulation of Circular Antigen-Specific T Cells Anergy in Autoimmune Vitiligo
AUTHORS:
Atsushi Tanemura, Lingli Yang, Ichiro Katayama
KEYWORDS:
Autoimmune Vitiligo, T Cell Anergy, Functional Regulatory T Cell
JOURNAL NAME:
Journal of Cosmetics, Dermatological Sciences and Applications,
Vol.8 No.3,
September
20,
2018
ABSTRACT: Background: Vitiligo is an autoimmune disorder related to melanocyte loss; however,
the exact interplay between antigen-specific autoimmunity and local oxidative
stress remains unclear. Recently, the migration ability and number of Foxp3-expressing
regulatory T cells (Tregs) in lesional skin was found to be reduced in vitiligo
patients. Objectives: We aimed to clarify the T cell anergy status of
melanocytes by focusing on the impaired equivalence of peripheral
melanocyte-specific cytotoxic T cells and functional Tregs in patients with
progressive vitiligo. Materials and methods: Ten progressive vitiligo
patients and 10 age-matched healthy individuals were enrolled in this study. We
analyzed the number of functional Tregs in progressive vitiligo patients and
compared the findings with those of controls. Next, to assess the suppressive
activity of Tregs on melanocyte-specific T lymphocytes, we strictly purified
the functional Tregs fraction and Melan-A-specific CD8+ T cells and
co-cultured these cells with each other. The number of Melan-A-specific CD8+ T cells was then counted by FACS. In addition, the expression of the
representative exhaustion markers PD-1 and CTLA-4 on functional Tregs was
assessed in vitiligo patients and normal controls. Results: The number of
functional Tregs itself was not significantly decreased in the blood of
vitiligo patients compared to healthy controls. However, the cytotoxic T cell
(CTL) proliferation was significantly decreased after cultivation with Tregs from
healthy individuals (p Conclusions: We
demonstrated a reduced suppressive function of activated Tregs on
Melan-A-specific CTLs in the circulating cells of vitiligo patients compared
with healthy controls. This result suggests that T cell anergy with Tregs
dysfunction may participate in the immune response to melanocytes in vitiligo
patients.