Axons are injured by antigen-specific CD8(+) T cells through a MHC class I- and granzyme B-dependent mechanism.

ABSTRACT: Axon injury is a central determinant of irreversible neurological deficit and disease progression in patients with multiple sclerosis (MS). CD8(+) lymphocytes (CTLs) within inflammatory demyelinated MS lesions correlate with acute axon injury and neurological deficits. The mechanisms of these correlations are unknown. We interrogated CTL-mediated axon injury using the transgenic OT-I antigen-specific CTL model system in conjunction with a chambered cortical neuron culture platform that permitted the isolated manipulation of axons independent of neuron cell bodies and glia. Interferon gamma upregulated, through a dose dependent mechanism, the axonal expression of functional major histocompatibility complex class I (MHC I) molecules competent to present immunologically-relevant antigens deri

SUBMITTER: Sauer BM 

PROVIDER: S-EPMC3788647 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature