Isolation and characterization of CD8+ regulatory T cells in multiple sclerosis

J Neuroimmunol. 2008 Mar;195(1-2):121-34. doi: 10.1016/j.jneuroim.2007.12.004. Epub 2008 Jan 30.


To investigate CD8+ regulatory T cell influence on multiple sclerosis development, peripheral blood and cerebrospinal fluid (CSF) CD8+ T cell clones (TCCs) recognizing MBP(83-102) and MOG(63-87)-specific CD4+ T cells were isolated from 20 patients during acute exacerbations, 15 in remission and 15 controls. Blood and CSF CD8+ regulatory TCC cloning frequency decreased more during exacerbations than remissions or controls. Target cell pre-activation significantly enhanced CD8+ T granule-mediated cell killing of CD4+ targets, and was restricted by HLA-E. During exacerbations, killer-inhibitory receptor CD94/NKG2A expression was significantly higher in CD8+ TCCs, limiting their cytotoxic activity. Moreover, IL-15 and IFN-gamma significantly increased CD94 and NKG2A expression. These data provide evidence that CD94/NKG2A receptors play an important role in regulating T cell activity during the course of MS.

MeSH terms

  • Adult
  • CD28 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / metabolism
  • Female
  • Flow Cytometry
  • Granzymes / pharmacology
  • Humans
  • Lymphocyte Activation / drug effects
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / pathology*
  • Myelin Basic Protein / pharmacology
  • NK Cell Lectin-Like Receptor Subfamily C
  • NK Cell Lectin-Like Receptor Subfamily D / metabolism
  • Peptide Fragments / pharmacology
  • Perforin / pharmacology
  • Receptors, Immunologic / metabolism
  • Receptors, Natural Killer Cell
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism*


  • CD28 Antigens
  • Cytokines
  • KLRC1 protein, human
  • Myelin Basic Protein
  • NK Cell Lectin-Like Receptor Subfamily C
  • NK Cell Lectin-Like Receptor Subfamily D
  • Peptide Fragments
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • Perforin
  • Granzymes