Murine autoimmune hearing loss mediated by CD4+ T cells specific for inner ear peptides
AUTOR(ES)
Solares, C. Arturo
FONTE
American Society for Clinical Investigation
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=385394Documentos Relacionados
- Multiple Effector Functions Mediated by Human Immunodeficiency Virus-Specific CD4+ T-Cell Clones
- Apoptotic depletion of CD4+ T cells in idiopathic CD4+ T lymphocytopenia.
- Changes in Murine Jejunal Morphology Evoked by the Bacterial Superantigen Staphylococcus aureus Enterotoxin B Are Mediated by CD4+ T Cells
- CD4+ T Cells in the Pathogenesis of Murine Ocular Toxoplasmosis
- Soluble HLA-G protein secreted by allo-specific CD4+ T cells suppresses the allo-proliferative response: A CD4+ T cell regulatory mechanism