CCR6+ Th cells in the cerebrospinal fluid of persons with multiple sclerosis are dominated by pathogenic non-classic Th1 cells and GM-CSF-only-secreting Th cells

Considerable attention has been given to CCR6(+) IL-17-secreting CD4(+) T cells (Th17) in the pathology of a number of autoimmune diseases including multiple sclerosis (MS). However, other Th subsets also play important pathogenic roles, including those that secrete IFN gamma and GM-CSF. CCR6 expression by Th17 cells allows their migration across the choroid plexus into the cerebrospinal fluid (CSF), where they are involved in the early phase of experimental autoimmune encephalomyelitis (EAE), and in MS these cells are elevated in the CSF during relapses and contain high frequencies of autoreactive cells. However, the relatively low frequency of Th17 cells suggests they cannot by themselves account for the high percentage of CCR6(+) cells in MS CSF. Here we identify the dominant CCR6(+) T cell subsets in both the blood and CSF as non-classic Th1 cells, including many that secrete GM-CSF, a key encephalitogenic cytokine. In addition, we show that Th cells secreting GM-CSF but not IFNy or IL-17, a subset termed GM-CSFonly-secreting Th cells, also accumulate in the CSF. Importantly, in MS the proportion of IFN gamma- and GM-CSF-secreting T cells expressing CCR6 was significantly enriched in the CSF, and was elevated in MS, suggesting these cells play a pathogenic role in this disease. (C) 2017 The Authors. Published by Elsevier Inc.