Two subsets of dendritic cells are present in human cerebrospinal fluid

Abstract

Little is known about the presence of dendritic cells in the human CNS. To investigate the occurrence of dendritic cells in the CSF, paired blood/CSF samples from patients with multiple sclerosis, acute optic neuritis, Lyme neuroborreliosis, other inflammatory neurological diseases and non-inflammatory neurological diseases were examined using flow cytometry. Almost all CSF samples contained myeloid (lin^–CD11c⁺HLA-DR⁺⁺CD123^dim) and plasmacytoid (lin^–CD11c^–HLA-DR⁺CD123^high) dendritic cells. In non-inflammatory neurological diseases, dendritic cells of either subset only constituted up to 1% of CSF mononuclear cells. Myeloid CSF dendritic cells were elevated in optic neuritis, neuroborreliosis and other inflammatory neurological disorders, while plasmacytoid dendritic cells were elevated in all neuroinflammatory conditions studied, with especially high numbers in neuroborreliosis. Numbers of CSF dendritic cells correlated with the common parameters of CNS inflammation. The myeloid dendritic cells in CSF expressed higher levels of HLA-DR, CD86, CD80 and CD40 than those in blood, whereas expression of these molecules by plasmacytoid dendritic cells was equal in blood and CSF. Both CSF and blood dendritic cells expressed the chemokine receptor CCR5. This is the first demonstration that dendritic cells are present in human CSF and that plasmacytoid dendritic cells are present in a non-lymphoid compartment. Myeloid and plasmacytoid dendritic cells in CSF may contribute to orchestration of the local immune responses.