Enriched CD161high CCR6+ γδ T cells in the cerebrospinal fluid of patients with multiple sclerosis

JAMA Neurol. 2013 Mar 1;70(3):345-51. doi: 10.1001/2013.jamaneurol.409.

Abstract

Objective: To investigate the expression of CD161 (KLRB1) and CCR6 on human γδ T cells in blood and cerebrospinal fluid (CSF) of patients with a clinically isolated syndrome (CIS) and multiple sclerosis (MS) in relapse.

Design: Flow cytometry analysis of CD161 and CCR6 expression and intracellular cytokine staining for interleukin 17 and interferon-γ on human γδ T cells in blood and CSF samples.

Setting: Department of Neurology, Klinikum rechts der Isar, Technische Universität München, a tertiary referral center.

Patients: Twenty-six patients with CIS/MS in active relapse, 10 patients with other autoimmune disorders, 12 patients with neuroinfectious diseases, and 15 patients with noninflammatory neurological diseases.

Main outcome measures: Frequencies of CD161high and CCR6+ γδ T cells in blood and CSF samples of patients with CIS/MS in relapse and control patients.

Results: γδ T cells were increased in both blood and CSF of patients with CIS/MS in relapse as compared with controls with noninflammatory disease. The fraction of CD161high CCR6+ γδ T cells was significantly higher in the CSF of patients with CIS/MS in relapse than of those with systemic autoimmune disorders or controls with noninflammatory disease. The CD161high CCR6+ double-positive γδ T-cell population was further enriched in the CSF in relation to blood in patients with CIS/MS in relapse but not in patients with infectious disease or the other control groups. The CD161high CCR6+ γδ T-cell population was characterized by its capacity to produce interleukin 17.

Conclusion: Interleukin 17–producing CD161high CCR6+ γδ T cells might contribute to the compartmentalized inflammatory process in the central nervous system of patients with MS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Female
  • Humans
  • Inflammation / cerebrospinal fluid
  • Inflammation / metabolism
  • Inflammation / pathology
  • Interleukin-17 / blood
  • Interleukin-17 / cerebrospinal fluid
  • Male
  • Middle Aged
  • Multiple Sclerosis / cerebrospinal fluid*
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / pathology
  • NK Cell Lectin-Like Receptor Subfamily B / biosynthesis*
  • Receptors, Antigen, T-Cell, gamma-delta / biosynthesis*
  • Receptors, CCR6 / biosynthesis*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocyte Subsets / pathology

Substances

  • Biomarkers
  • CCR6 protein, human
  • Interleukin-17
  • KLRB1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily B
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, CCR6