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Neuronal MHC-I display in T-cell mediated neurodegeneration
© Cebrián et al; licensee BioMed Central Ltd. 2013
Published: 13 September 2013
Parkinson’s disease (PD) and other disorders feature the degeneration of ventral midbrain (VM) catecholamine neurons. Recent data suggest that neuroinflammatory mechanisms contribute to a cascade of events leading to chronic neuronal degeneration.
In primary murine neuronal cultures, substantia nigra (SN) and locus coeruleus (LC) neurons are induced to express the major histocompatibility class I complex (MHC-I) by the proinflammatory cytokine, γ-interferon, L-DOPA, or conditioned medium from microglia exposed to α-synuclein or NM. SN DA neurons, moreover, process the foreign protein ovalbumin to an antigenic peptide that is presented by their MHC-I and triggers their specific destruction by CD8+ killer T-cells. In human postmortem samples, we find by immunolabel, mRNA profiling, and proteomic analysis that neuromelanin (NM)-containing catecholamine SN and LC neurons in adult human control and PD brains express MHC-I, often in proximity to CD8+ T-cells. These data reveal a novel inflammatory T-cell mediated neurodegenerative processes that could underlie neuronal death.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.