CD161highCD8+T cells bear pathogenetic potential in multiple sclerosis

Viviana Annibali, Giovanni Ristori, Daniela F. Angelini, Barbara Serafini, Rosella Mechelli, Stefania Cannoni, Silvia Romano, Andrea Paolillo, Hadi Abderrahim, Adamo Diamantini, Giovanna Borsellino, Francesca Aloisi, Luca Battistini, Marco Salvetti

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)542-554
Number of pages13
JournalBrain
Volume134
Issue number2
DOIs
Publication statusPublished - Feb 2011

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Keywords

  • CCR6
  • CD161
  • gene expression
  • IL-17
  • multiple sclerosis

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Annibali, V., Ristori, G., Angelini, D. F., Serafini, B., Mechelli, R., Cannoni, S., Romano, S., Paolillo, A., Abderrahim, H., Diamantini, A., Borsellino, G., Aloisi, F., Battistini, L., & Salvetti, M. (2011). CD161highCD8+T cells bear pathogenetic potential in multiple sclerosis. Brain, 134(2), 542-554. https://doi.org/10.1093/brain/awq354