Journal
AUTOIMMUNITY REVIEWS
Volume 5, Issue 7, Pages 486-492Publisher
ELSEVIER
DOI: 10.1016/j.autrev.2006.03.012
Keywords
melanocytes; T cells; T cell avidity; T cell receptors; melanosomes; antigen presentation
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Funding
- NCI NIH HHS [R01 CA109636, R01 CA090873, R01 CA109536, CA90873] Funding Source: Medline
- NIAMS NIH HHS [R03 AR050137, R03 AR50137] Funding Source: Medline
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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 I-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. (c) 2006 Elsevier B.V. All rights reserved.
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