Clonotype analysis of alopecia areata-specific CD8 T-lymphocytes

Year: 
2013
PI Name: 
Ralf Paus, MD
Type:
Research Grant
Status: 
Complete

Summary

This project aims to characterize the receptors of the autoaggressive T‐cell clones that are responsible for alopecia areata by isolating CD8+ T cells from alopecia areata skin and identify their T‐cell receptor chain directly in human skin with alopecia areata lesions.

Abstract

The autoimmune hair loss disorder, alopecia areata (AA), is thought to result from an autoaggressive attack of certain white blood cells (CD8+ T cells) against as yet unkown “self”-components (autoantigens) that are present in human hair follicles. We aim to characterize the receptors of the autoaggressive T-cell clones that are responsible for AA by isolating CD8+ T-cell from AA skin and by characterizing their T cell receptor (TCR) chain directly in human skin with AA lesions. Identification of disease-specific TCRs can then serve as a basis for specific AA immunotherapy and may serve as prognostic biomarker(s). Namely, this will allow us selectively eliminate autoaggressive CD8+ T-cell clones and to identify, in a follow-up project, the self-autoantigen(s) that trigger the attack on the HFs so that, eventually, affected patients can be tolerized against these autoantigen(s). If successful this will ultimately permit the first causal therapy of AA.

Impact

If successful, this study may lead to selective eliminatation of autoaggressive CD8+ T‐cell clones, identification of the self-autoantigens that trigger the attack on the hair follicles, and serve as a basis for AA immunotherapy and prognostic biomarker(s).

Publication

Bertolini M, Uchida Y, Paus R. Toward the Clonotype Analysis of Alopecia Areata-Specific, Intralesional Human CD8+ T Lymphocytes. J Investig Dermatol Symp Proc. 2015 Nov;17(2):9-12. doi: 10.1038/jidsymp.2015.31