Tolerance induction by hair-specific keratins in murine alopecia areata

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.