Murine autoimmune hearing loss mediated by CD4+ T cells specific for inner ear peptides
C. Arturo Solares, … , Gordon B. Hughes, Vincent K. Tuohy
C. Arturo Solares, … , Gordon B. Hughes, Vincent K. Tuohy
Published April 15, 2004
Citation Information: J Clin Invest. 2004;113(8):1210-1217. https://doi.org/10.1172/JCI18195.
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Article Autoimmunity

Murine autoimmune hearing loss mediated by CD4+ T cells specific for inner ear peptides

Abstract

Autoimmune sensorineural hearing loss (ASNHL) is characterized typically by bilateral, rapidly progressive hearing loss that responds therapeutically to corticosteroid treatment. Despite its name, data implicating autoimmunity in the etiopathogenesis of ASNHL have been limited, and targeted self-antigens have not been identified. In the current study we show that the inner ear–specific proteins cochlin and β-tectorin are capable of targeting experimental autoimmune hearing loss (EAHL) in mice. Five weeks after immunization of SWXJ mice with either Coch 131–150 or β-tectorin 71–90, auditory brainstem responses (ABR) showed significant hearing loss at all frequencies tested. Flow cytometry analysis showed that each peptide selectively activated CD4+ T cells with a proinflammatory Th1-like phenotype. T cell mediation of EAHL was determined by showing significantly increased ABR thresholds 6 weeks after adoptive transfer of peptide-activated CD4+ T cells into naive SWXJ recipients. Immunocytochemical analysis showed that leukocytic infiltration of inner ear tissues coincided with onset of hearing loss. Our study provides a contemporary mouse model for clarifying our understanding of ASNHL and facilitating the development of novel effective treatments for this clinical entity. Moreover, our data provide experimental confirmation that ASNHL may be a T cell–mediated organ-specific autoimmune disorder of the inner ear.

Authors

C. Arturo Solares, Andrea E. Edling, Justin M. Johnson, Moo-Jin Baek, Keiko Hirose, Gordon B. Hughes, Vincent K. Tuohy

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Figure 3

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T cell responses to Coch 131–150 and β-tectorin 71–90 are restricted by ...
T cell responses to Coch 131–150 and β-tectorin 71–90 are restricted by IAs and IAq, respectively. Eight to 10 days after immunization of female SWXJ (H-2q,s), SWR/J (H-2q), and SJL/J (H-2s) mice with either Coch 131–150 or β-tectorin 71–90, LN cells were tested for elicitation of recall proliferative responses to 100 μg/ml of each peptide. (A) LN cells from primed SWXJ mice responded to each peptide. (B) LN cells from primed SJL/J mice responded to Coch 131–150 but did not respond to β-tectorin 71–90, whereas (C) LN cells from primed SWR/J mice responded to β-tectorin 71–90 but did not respond to Coch 131–150. Thus, responses to Coch 131–150 showed restriction by IAs, whereas responses to β-tectorin 71–90 showed restriction by IAq. Error bars show ± SE.