Therapeutic implications of autoimmune vitiligo T cells.
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.
Oyarbide-Valencia
Kepa
K
Department of Pathology/Oncology Institute, Loyola University Chicago, 2160 South First Ave, Bldg 112, Rm 203, Maywood, IL 60153, USA.
van den Boorn
Jasper G
JG
Denman
Cecele J
CJ
Li
Mingli
M
Carlson
Jeremy M
JM
Hernandez
Claudia
C
Nishimura
Michael I
MI
Das
Pranab K
PK
Luiten
Rosalie M
RM
Le Poole
I Caroline
IC
D000818:Animals; D006801:Humans; D008545:Melanoma / Q000276:immunology* / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D014820:Vitiligo / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell