Cerebrospinal fluid affects phenotype and functions of myeloid dendritic cells

Abstract

SUMMARYMyeloid (CD11c + ) dendritic cells (DC) are present in cerebrospinal fluid (CSF), as well as in the meninges and choroid plexus. Functional studies of these DC are hindered or impossible. To obviate this problem, we investigated the effects of CSF supernatants from patients with non-inflammatory neurological diseases (NIND), multiple sclerosis (MS), bacterial meningitis (BM) and Lyme meningoencephalitis (LM) on immature monocyte-derived DC (moDC) from healthy donors. CSF supernatants caused maturation of moDC (MS > LM > NIND > BM), as reflected by a decrease in CD1a, and an increase in HLA-DR, CD80 and CD86 expression. The maturation effect of MS CSF and LM CSF could be blocked by anti-TNF-a MoAb or recombinant human IL-10. moDC cultured with BM CSF either remained immature or turned into CD14 + macrophage-like cells and were relatively inefficient at inducing T cell responses in vitro. In contrast, moDC cultured with LM CSF induced strong Th1 responses. Both BM CSF and LM CSF contained IFN-g, a cytokine that augments IL-12 production by moDC and hence should confer an ability to induce a Th1 response. However, BM CSF also contained high levels of IL-10, which could antagonize the effects of IFN-g on moDC. moDC cultured with MS CSF induced a higher production of IFN-g from T cells compared to moDC cultured with NIND CSF or BM CSF. In summary, soluble factors present in the CSF may influence the phenotype and functions of meningeal, choroid plexus and CSF DC which, in turn, may have an impact on the character of intrathecal T cell responses.

Central memory CD4+ T cells dominate the normal cerebrospinal fluid

“…In addition to the relatively high frequency of dendritic cells in CSF, we found a predominance of myeloid over plasmacytoid dendritic cells which may be explained by the origin of dendritic cells in CSF. Most myeloid dendritic cells arise in the CNS from blood monocytes (26), while plasmacytoid dendritic cells are all blood-borne (27). Dendritic cells are the most potent antigen presenting cells (28).…”

“…Dendritic cells are the most potent antigen presenting cells (28). In CSF they take up antigens that invade the CNS and present them to T cells in secondary lymphoid organs, such as deep cervical lymph nodes (27). In this way, dendritic cells have an important role in the adaptive immune response in CSF.…”

Dendritic Cell Transmigration through Brain Microvessel Endothelium Is Regulated by MIP-1α Chemokine and Matrix Metalloproteinases

“…Although DCs could develop from microglia in the brain (2,3) or be found as resident cells in the CNS (4,5), they also infiltrate into the CNS from the blood (1). The mechanism of DC infiltration into the CNS is yet to be determined.…”

Modulation of dendritic cell development by immunoglobulin G in control subjects and multiple sclerosis patients

“…Several reports on relapsing-remitting multiple sclerosis (RR-MS) assert that monocyte-derived DCs (Mo-DCs) release matrixdegrading metalloproteinases (MMP)-9 and are involved in the disruption of nerve tissues [20]. In addition, the spinal fluid of relapsing MS patients may contain some soluble factors that promote the differentiation of Mo-DCs [21], implicating Mo-DCs in MS relapses. Duddy et al argued that Mo-DCs may be a therapeutic target cells in MS, because current effective therapies, including interferon (IFN)-b and steroids, inhibit the differentiation of monocytes into DCs [22].…”