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J Leukoc Biol. 2013 Oct;94(4):845-57. doi: 10.1189/jlb.0413196. Epub 2013 Jul 1.

Tolerance induction by hair-specific keratins in murine alopecia areata.

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1
1.University Hospital of Surgery, Im Neuenheimer Feld 365, D 69120 Heidelberg, Germany. margot.zoeller@uni-heidelberg.de.

Abstract

AA is a presumptive autoimmune disease, severely damaging the hair follicle. Hair- and nail-specific keratins are discussed as potential candidates, which we controlled in C3H/HeJ mice that develop AA spontaneously or after skin transplantation. From nine keratins, K71 and K31 peptides supported T cell activation when presented by DCs to syngeneic naive T cells, and young C3H/HeJ mice receiving s.c. injections of peptide-loaded DC developed AA. The frequency of K71- and K31-specific CD4(+) and CD8(+) T cells increased four- to fivefold by vaccination, which corresponds with the frequency seen in skin transplantation-induced AA mice. Also, accessory molecule expression, the cytokine profile with a dominance of IFN-γ-expressing T cells, the proliferative response against AA lysate or peptide-loaded DCs, as well as peptide-specific cytotoxic T cells were similar in keratin peptide- and skin transplantation-induced AA. Instead, vaccination with soluble K71 or K31 peptides significantly retarded AA induction and prevented progression. Soluble peptide vaccination did not provoke immunosuppression but induced long-lasting T cell anergy with unresponsiveness to DC-presented K71 and K31 peptides. Thus, keratins K71 and K31 contribute to AA induction, and peptide application in a nonimmunogenic form serves as an efficient therapeutic.

KEYWORDS:

autoantigen; mouse; therapy; vaccination

PMID:
23817565
DOI:
10.1189/jlb.0413196
[Indexed for MEDLINE]
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