Experimental autoimmune hearing loss

Abstract

Understanding of autoimmune sensorineural hearing loss (ASNHL) has been hindered by the inaccessibility of the inner ear to biopsy and the lack of workable animal models. A report in this issue of the JCI describes a mouse model of CD4(+) T cell-mediated ASNHL induced by immunization with peptides from the inner ear-specific proteins cochlin and beta-tectorin.

Figure 1

Systemic immunization of autoimmune-prone SWXJ mice with Coch 131–150, an RXXS peptide from the abundant IE extracellular protein cochlin, induced CD45⁺ cell cochlear infiltration and ASNHL in mice within 5–6 weeks. Lymph node (LN) or spleen cells placed in culture 8–10 days after immunization proliferated, as evidenced by ³H-thymidine incorporation, and showed a Th1 cytokine profile (high levels of IFN-γ and low levels of IL-4 production) after restimulation in vitro with Coch 131–150. Flow cytometry confirmed preferential reactivation of CD4⁺ T cells. After restimulation in vitro with peptide, the total population or the CD4⁺-enriched population (>95%) of cells induced ASNHL 6 weeks after passive transfer to naive, irradiated, histocompatible recipient mice. The same results were obtained after priming, restimulation, and transfer of CD4⁺ T cells specific for a KXXS peptide from a second IE protein, β-tectorin 71–90, but not with ovalbumin as Ag (16).