Therapeutic implications of autoimmune vitiligo T cells

被引:85
作者
Oyarbide-Valencia, Kepa
van den Boorn, Jasper G.
Denman, Cecele J.
Li, Mingli
Carlson, Jeremy M.
Hernandez, Claudia
Nishimura, Michael I.
Das, Pranab K.
Luiten, Rosalie M.
Le Poole, I. Caroline
机构
[1] Loyola Univ, Inst Oncol, Dept Pathol, Maywood, IL 60153 USA
[2] Univ Amsterdam, Dept Dermatol, Amsterdam, Netherlands
[3] Univ Amsterdam, SNIP, Amsterdam, Netherlands
[4] Univ Illinois, Dept Dermatol, Chicago, IL USA
[5] Univ Amsterdam, Dept Pathol, Amsterdam, Netherlands
关键词
melanocytes; T cells; T cell avidity; T cell receptors; melanosomes; antigen presentation;
D O I
10.1016/j.autrev.2006.03.012
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:486 / 492
页数:7
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