The co-inhibitory molecule PD-1 modulates disease severity in a model for an inherited, demyelinating neuropathy

• Main Authors: Antje Kroner, Nicholas Schwab, Chi Wang Ip, Claudia Sommer, Carsten Wessig, Heinz Wiendl, Rudolf Martini
• Format: Article
• Language: English
• Published: Elsevier 2009-01-01
• Series: Neurobiology of Disease
• Subjects: Schwann cell; Charcot-Marie-Tooth disease; Myelin; T-lymphocytes; Adaptive immune system; Macrophages
• Online Access: http://www.sciencedirect.com/science/article/pii/S0969996108002301

We have previously shown that mice heterozygously deficient for P0 are characterized by a late onset myelin disorder implicating CD8+ T-lymphocytes and macrophages. We now investigated the impact of the co-inhibitory molecule “programmed death” (PD)-1 (CD279), a CD28-related receptor expressed on activated T- and B-lymphocytes on the pathogenic phenotype of CD8+ T-lymphocytes in the P0 myelin mutants. PD-1 deficiency in P0+/− mice leads to a stronger increase of CD8+ T-lymphocytes and a substantially aggravated histological phenotype in the PNS compared to P0+/− mice expressing PD-1. Correspondingly, functional down-stream features, such as electrophysiological parameters, walking coordination and mechano-sensation are more affected than in PD-1-expressing myelin mutants. Our study demonstrates that a monogenic nerve disorder can be substantially modified by immune-controlling mechanisms. Thus, understanding the implication of disease-modifiers in inherited demyelination could be of pivotal interest for limiting the detrimental impact of primarily genetically-mediated myelin disorders by fostering immuno-regulatory pathways.