The Immune Response In PLP-Overexpressing Mice

This week, Ip et al. examined mice that overexpress the myelin component proteolipid protein (PLP) and display late-onset demyelination. The authors report that primary glial damage caused a secondary immune response that contributes to the pathology. CD8-expressing T-lymphocytes were upregulated in the PLP transgenic mice, and the T-cells were closely associated with major histocompatibility complex I (MHC-I). The authors surmised that MHC-I+ mutant oligodendrocytes were targeted by T-cells. Flow cytometry experiments confirmed that the brain CD8+ cells were activated mature effector cells. The authors crossed the PLP mice with mice deficient for recombination activating gene-1 (RAG-1) that lack mature T- and B-lymphocytes. Demyelination was reduced in these mice, an effect that was reversed by implantation of CD8+/CD4− bone marrow, indicating that the CD8+ lymphocytes are important to the secondary immune response. The authors suggest that this pattern of secondary, rather than primary, inflammatory/immune response may also underlie some subtypes of multiple sclerosis.

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Chi Wang Ip, Antje Kroner, Martin Bendszus, Christoph Leder, Igor Kobsar, Stefan Fischer, Heinz Wiendl, Klaus-Armin Nave, and Rudolf Martini

Source: News tips from the Journal of Neuroscience

Contact: Sara Harris
Society for Neuroscience
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The Immune Response In PLP-Overexpressing Mice