Murine autoimmune hearing loss mediated by CD4+ T cells specific for inner ear peptides.
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 beta-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 beta-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.
Solares
C Arturo
CA
Department of Immunology, and Head and Neck Institue, Cleveland Clinic Foundation, Ohio 44195, USA.
Edling
Andrea E
AE
Johnson
Justin M
JM
Baek
Moo-Jin
MJ
Hirose
Keiko
K
Hughes
Gordon B
GB
Tuohy
Vincent K
VK
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D001665:Binding Sites; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000209:etiology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007114:Immunization; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D011506:Proteins / Q000276:immunology*
C491729:Coch protein, mouse; D016326:Extracellular Matrix Proteins; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D011506:Proteins