Enriched CD161high CCR6+ γδ T Cells in the Cerebrospinal Fluid of Patients With Multiple Sclerosis

Objective: To investigate the expression of CD161 (KLRB1) and CCR6 on human gamma delta 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-gamma on human gamma delta T cells in blood and CSF samples. Setting: Department of Neurology, Klinikum rechts der Isar, Technische Universitat Munchen, 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 CD161(high) and CCR6(+) gamma delta T cells in blood and CSF samples of patients with CIS/MS in relapse and control patients. Results: gamma delta 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 CD161(high) CCR6(+) gamma delta 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 CD161(high) CCR6(+) doublepositive gamma delta 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 CD161(high) CCR6(+) gamma delta T-cell population was characterized by its capacity to produce interleukin 17. Conclusion: Interleukin 17-producing CD161(high) CCR6(+) gamma delta T cells might contribute to the compartmentalized inflammatory process in the central nervous system of patients with MS. JAMA Neurol. 2013;70(3):345-351. Published online December 17, 2012. doi: 10.1001/2013.jamaneurol.409