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

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

Research output: Contribution to journalArticle

55 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1210-1217
Number of pages8
JournalJournal of Clinical Investigation
Volume113
Issue number8
DOIs
StatePublished - Apr 1 2004

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Inner Ear
Hearing Loss
Sensorineural Hearing Loss
T-Lymphocytes
Peptides
Brain Stem Auditory Evoked Potentials
Adoptive Transfer
Autoantigens
Autoimmunity
Names
Immunization
Flow Cytometry
Adrenal Cortex Hormones
Phenotype
Therapeutics
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Solares, C. A., Edling, A. E., Johnson, J. M., Baek, M. J., Hirose, K., Hughes, G. B., & Tuohy, V. K. (2004). Murine autoimmune hearing loss mediated by CD4+ T cells specific for inner ear peptides. Journal of Clinical Investigation, 113(8), 1210-1217. https://doi.org/10.1172/JCI200418195

Murine autoimmune hearing loss mediated by CD4+ T cells specific for inner ear peptides. / Solares, Clementino Arturo; Edling, Andrea E.; Johnson, Justin M.; Baek, Moo Jin; Hirose, Keiko; Hughes, Gordon B.; Tuohy, Vincent K.

In: Journal of Clinical Investigation, Vol. 113, No. 8, 01.04.2004, p. 1210-1217.

Research output: Contribution to journalArticle

Solares, CA, Edling, AE, Johnson, JM, Baek, MJ, Hirose, K, Hughes, GB & Tuohy, VK 2004, 'Murine autoimmune hearing loss mediated by CD4+ T cells specific for inner ear peptides', Journal of Clinical Investigation, vol. 113, no. 8, pp. 1210-1217. https://doi.org/10.1172/JCI200418195
Solares CA, Edling AE, Johnson JM, Baek MJ, Hirose K, Hughes GB et al. Murine autoimmune hearing loss mediated by CD4+ T cells specific for inner ear peptides. Journal of Clinical Investigation. 2004 Apr 1;113(8):1210-1217. https://doi.org/10.1172/JCI200418195
Solares, Clementino Arturo ; Edling, Andrea E. ; Johnson, Justin M. ; Baek, Moo Jin ; Hirose, Keiko ; Hughes, Gordon B. ; Tuohy, Vincent K. / Murine autoimmune hearing loss mediated by CD4+ T cells specific for inner ear peptides. In: Journal of Clinical Investigation. 2004 ; Vol. 113, No. 8. pp. 1210-1217.
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