Autoimmune-mediated inner ear inflammation in mice immunized with coch-5B2

Abstract

Problem: We have shown that SWXJ mice develop hearing loss when immunized with the p131–150 peptide of Coch-5B2 or following transfer of activated T cells specific for the Coch 131–150 peptide. Further studies to establish associated histopathology in the cochleas of these mice were pursued in this paper. Methods: Mice were immunized with Coch 131–150 in complete Freund’s adjuvant (CFA) and euthanized 2–5 weeks later. Inner ear tissues were immunostained for detection of inflammatory cells. ABR testing to determine hearing thresholds was performed on Coch 131–150 primed mice and on age- and sex-matched control mice immunized with CFA only. Results: Inner ear inflammation was observed 5 weeks after active immunization with Coch 131–150, but not at 2, 3, or 4 weeks. Increased ABR thresholds were accompanied by substantial CD45+ immunostaining in the lower spiral ligament primarily in the high frequency region of the cochlea. Control animals showed no increase in ABR thresholds and no inner ear inflammation. Conclusion: Induction of experimental autoimmune hearing loss in mice by immunization with Coch 131–150 results in appearance of leukocytes in the inner ear. The current data support our previously reported findings that Coch-5B2 targets T cell-mediated hearing loss in SWXJ mice. Significance: Our study shows that T cells targeted against inner ear-specific antigens may mediate inner ear inflammation and hearing loss in the mouse similar to that observed in human autoimmune sensorineural hearing loss (ASNHL). Thus, our study supports a critical role of autoreactive T cells in ASNHL and provides a contemporary mouse model for evaluating new treatment strategies. Support: Grants from the Deafness Research Foundation, the Samuel Rosenthal Foundation, the Triple T Foundation, the Milton and Charlotte Kramer Foundation, and NIH NS-36054.