Immunopolarization of CD4+ and CD8+ T cells to Type-1-like is associated with melanocyte loss in human vitiligo.
Vitiligo is an autoimmune condition characterized by loss of epidermal melanocytes. High frequencies of melanocyte-reactive cytotoxic T cells in the peripheral blood of vitiligo patients and the observed correlation between perilesional T-cell infiltration and melanocyte loss in situ suggest the important role of cellular autoimmunity in the pathogenesis of this disease. We isolated T cells from both perilesional and nonlesional skin biopsies obtained from five vitiligo patients, then cloned and analyzed their profile of cytokine production after short-term, nonspecific expansion in vitro. Perilesional T-cell clones (TCC) derived from patients with vitiligo exhibited a predominant Type-1-like cytokine secretion profile, whereas the degree of Type-1 polarization in uninvolved skin-derived TCC correlated with the process of microscopically observed melanocyte destruction in situ. Detailed analysis of broad spectrum of cytokines produced by perilesional- and nonlesional-derived CD4+ and CD8+ TCC confirmed polarization toward Type-1-like in both CD4 and CD8 compartments, which paralleled depigmentation process observed locally in the skin. Furthermore, CD8+ TCC derived from two patients also were analyzed for reactivity against autologous melanocytes. The antimelanocyte cytotoxic reactivity was observed among CD8+ TCC isolated from perilesional biopsies of two patients with vitiligo. Finally, in two of five patients, tetramer analysis revealed presence of high frequencies of Mart-1-specific CD8 T cells in T-cell lines derived from perilesional skin. Altogether our data support the role of cellular mechanisms playing a significant part in the destruction of melanocytes in human autoimmune vitiligo.
Department of Pathology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
Anna
A
Wańkowicz-Kalińska
René M J G J
RM
van den Wijngaard
Bert J
BJ
Tigges
Wiete
W
Westerhof
Graham S
GS
Ogg
Vincenzo
V
Cerundolo
Walter J
WJ
Storkus
Pranab K
PK
Das
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002460:Cell Line; D016764:Cell Polarity; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008297:Male; D008544:Melanocytes / Q000473:pathology*; D008875:Middle Aged; D012867:Skin / Q000473:pathology; D014820:Vitiligo / Q000276:immunology* / Q000473:pathology
D015847:Interleukin-4; D007371:Interferon-gamma