Monocytes represent a heterogeneous population of primary immune effector cells. At least three different subsets can be distinguished based on expression of the low-affinity FcγRIII: CD14++CD16− classical monocytes, CD14++CD16+ intermediate monocytes, and CD14+CD16++ non-classical monocytes. Whereas CD16− classical monocytes are considered key players in multiple sclerosis (MS), little is known on CD16+ monocytes and how they contribute to the disease. In this study, we examined the frequency and phenotype of monocyte subpopulations in peripheral blood, cerebrospinal fluid (CSF), and brain biopsy material derived from MS patients and controls. Furthermore, we addressed a possible monocyte dysfunction in MS and analyzed migratory properties of monocyte subsets using human brain microvascular endothelial cells. Our ex vivo studies demonstrated that CD16+ monocyte subpopulations are functional but numerically reduced in the peripheral blood of MS patients. CD16+ monocytes with an intermediate-like phenotype were found to be enriched in CSF and dominated the CSF monocyte population under noninflammatory conditions. In contrast, an inversed CD16+ to CD16− CSF monocyte ratio was observed in MS patients with relapsing-remitting disease. Newly infiltrating, hematogenous CD16+ monocytes were detected in a perivascular location within active MS lesions, and CD16+ monocytes facilitated CD4+ T cell trafficking in a blood–brain barrier model. Our findings support an important role of CD16+ monocytes in the steady-state immune surveillance of the CNS and suggest that CD16+ monocytes shift to sites of inflammation and contribute to the breakdown of the blood–brain barrier in CNS autoimmune diseases.

Summary T cells with a CD4

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CD45, also called leucocyte common antigen is a transmembrane protein tyrosine phosphatase on the surface of nearly all white blood cells and has a functional role in signal transduction. In the brain, the expression of CD45 can be used to distinguish microglial cells with a characteristic phenotype of CD11b/c+ and CD45(low) from other central nervous system (CNS) macrophages which show an expression of CD11b/c+ and CD45(high). In the course of pathological changes in the CNS, microglia in rodents is known to readily upregulate expression of various surface molecules, such as CD45. Understanding the mechanisms that regulate expression of surface molecules is essential to study the pathogenesis of CNS diseases. In the present study, the expression of CD45 on microglia of 42 dogs was examined ex vivo by means of flow cytometry. The dogs were classified in two groups according to the histopathological diagnosis in the CNS. All dogs without changes in the CNS (group I; n = 22) only showed low percentages of CD45+ microglial cells. In group II consisting of 20 dogs with different intracranial diseases varying results were obtained. Thirteen dogs showed a low percentage of CD45+ microglial cells whereas seven dogs exhibited high percentages of microglial cells expressing CD45. Evaluation of expression intensity in these seven dogs revealed two subpopulations of CD45+ microglial cells: a large subpopulation with CD45(low) and a small subpopulation with CD45(high). The expression intensity of CD45(high) was comparable with that of canine monocytes. It was attempted to correlate these findings to age of the animals, underlying disease, duration of clinical signs, medical treatment, occurrence of seizure activity and the expression of other surface molecules. It appeared that dogs with high percentages of CD45+ suffered from long-lasting CNS disease with seizures. In future studies, the reason and consequences for upregulated CD45 in long-lasting CNS diseases has to be further evaluated.