Therapeutic implications of autoimmune vitiligo T cells

Kepa Oyarbide-Valencia, Jasper G. van den Boorn, Cecele J. Denman, Mingli Li, Jeremy M. Carlson, Claudia Hernandez, Michael I. Nishimura, Pranab K. Das, Rosalie M. Luiten, I. Caroline Le Poole*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

63 Scopus citations

Abstract

Vitiligo is an autoimmune disease presenting with progressive loss of skin pigmentation. The disease strikes 1% of the world population, generally during teenage years. The progressive loss of melanocytes from depigmenting vitiligo skin is accompanied by cellular infiltrates containing both CD4+ and CD8+ T lymphocytes. Infiltrating cytotoxic T cells with high affinity T cell receptors have likely escaped clonal deletion in the thymus, allowing such T cells to enter the circulation. Through the expression of CLA, these T cells home to the skin where they express type 1-cytokine profiles and mediate melanocyte apoptosis via the granzyme/perforin pathway. T cells found juxtapositionally apposed to remaining melanocytes can be isolated from the skin. Vitiligo T cells have demonstrated reactivity to antigens previously recognized as target antigens for T cells infiltrating melanoma tumors. In a comparison to existing melanoma-derived T cells, vitiligo T cells displayed superior reactivity towards melanoma cells. It is thought that genes encoding the TCRs expressed by vitiligo skin infiltrating T cells can be cloned and expressed in melanoma T cells, thereby generating a pool of circulating T cells with high affinity for their targets that can re-direct the immune response towards the tumor.

Original languageEnglish (US)
Pages (from-to)486-492
Number of pages7
JournalAutoimmunity Reviews
Volume5
Issue number7
DOIs
StatePublished - Aug 2006

Keywords

  • Antigen presentation
  • Melanocytes
  • Melanosomes
  • T cell avidity
  • T cell receptors
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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