CD161highCD8+T cells bear pathogenetic potential in multiple sclerosis
Open Access
- 7 January 2011
- journal article
- research article
- Published by Oxford University Press (OUP) in Brain
- Vol. 134 (2), 542-554
- https://doi.org/10.1093/brain/awq354
Abstract
To identify differentially expressed genes in multiple sclerosis, microarrays were used in a stringent experimental setting—leukapheresis from disease-discordant monozygotic twins and gene expression profiling in CD4+ and CD8+ T-cell subsets. Disease-related differences emerged only in the CD8+ T-cell subset. The five differentially expressed genes identified included killer cell lectin-like receptor subfamily B, member 1, also known as natural killer receptor protein 1a/CD161, presented by the International Multiple Sclerosis Genetics Consortium as one of the non-MHC candidate loci. Flow cytometric analysis on peripheral blood of healthy donors and patients with multiple sclerosis and rheumatoid arthritis confirmed an upregulation of CD161 at the protein level, showing also a significant excess of CD161highCD8+ T cells in multiple sclerosis. This subset prevalently included chemokine (C-C motif) receptor 6+, cytokine-producing, effector-memory T cells with proinflammatory profiles. It also included all circulating interleukin-17+CD8+ T cells. In the CD161highCD8+ subset, interleukin-12 facilitated proliferation and interferon-γ production, with CD161 acting as a co-stimulatory receptor. CD161+CD8+CD3+ T cells producing interferon-γ were part of intralesional immune infiltrates and ectopic B cell follicles in autopsy multiple sclerosis brains. Variations of CD161 expression on CD8+ T cells identify a subset of lymphocytes with proinflammatory characteristics that have not been previously reported in multiple sclerosis and are likely to contribute to disease immunopathology.Keywords
This publication has 38 references indexed in Scilit:
- Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosisNature, 2010
- Analysis of CD161 expression on human CD8+T cells defines a distinct functional subset with tissue-homing propertiesProceedings of the National Academy of Sciences, 2010
- A Distinct Subset of Self-Renewing Human Memory CD8+ T Cells Survives Cytotoxic ChemotherapyImmunity, 2009
- Epstein–Barr virus infection is not a characteristic feature of multiple sclerosis brainBrain, 2009
- Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility lociNature Genetics, 2009
- Circulating and gut-resident human Th17 cells express CD161 and promote intestinal inflammationThe Journal of Experimental Medicine, 2009
- Multiple sclerosisThe Lancet, 2008
- Human interleukin 17–producing cells originate from a CD161+CD4+ T cell precursorThe Journal of Experimental Medicine, 2008
- A rush to judgment on Th17The Journal of Experimental Medicine, 2008
- Dysregulated Epstein-Barr virus infection in the multiple sclerosis brainThe Journal of Experimental Medicine, 2007