Two subsets of dendritic cells are present in human cerebrospinal fluid

Pashenkov, Мikhail; Huang, Yu‐Min; Kostulas, Vasilios; Haglund, Mats; Söderström, M.; Link, Hans

doi:10.1093/brain/124.3.480

Cited by 216 publications

(189 citation statements)

References 30 publications

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“…In NIND, relatively few myeloid DC are present in the meninges, choroid plexus and CSF (in CSF, they are < 50 cells/ml) [7], foreign antigens are absent, and the maturation effect of CSF on DC is rather weak. Even if these DC migrate to DCLN, they would cause little or no T cell activation.…”

Section: Discussionmentioning

confidence: 99%

“…In MS, presentation of MBPLM by more numerous and more mature DC bearing appropriate HLA molecules may further boost the autoaggressive Th1 response. Myeloid DC can reach up to 4% of total CSF cells (500 cells/ml) in ON -early MS -and up to 3% (400 cells/ml) in clinically definite MS [7,14]; thus, relatively high DC:T cell ratios may be maintained, e.g. in DCLN.…”

Section: Discussionmentioning

confidence: 99%

“…However, DC are present in substantial numbers in the meninges and choroid plexus [2][3][4][5][6]. We have shown recently that human cerebrospinal fluid (CSF) contains myeloid and plasmacytoid DC [7].…”

Section: Introductionmentioning

confidence: 99%

“…When the CNS is affected by inflammation, the numbers of DC in the meninges and CSF are increased, due most probably to active recruitment from the circulation [4,7,13,14]. DC accumulate in human CSF, in order of increasing numbers, in clinically definite multiple sclerosis (MS), acute monosymptomatic optic neuritis (ON), bacterial meningitis (BM) and Lyme meningoencephalitis (LM) [7,13]. The numbers of DC in the meninges and choroid plexus of these patients are not known, however they may correlate with those in the CSF.…”

Section: Introductionmentioning

confidence: 99%

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Cerebrospinal fluid affects phenotype and functions of myeloid dendritic cells

Pashenkov

Soderstrom

Huang

et al. 2002

Clinical and Experimental Immunology

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cerebrospinal fluid affects phenotype and functions of myeloid dendritic cells

Pashenkov

Soderstrom

Huang

et al. 2002

Clinical and Experimental Immunology

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“…[60][61][62] Moreover, circulating cDCs in RRMS show increased expression of activation markers and chemokine (C-C motif) receptor 5 (CCR5) than healthy controls. 63,64 Interestingly, the expression of the CCR5 ligands chemokine (C-C motif) ligand 3 (CCL3) and CCL5 is increased in MS CNS lesions, 65 and CCR5 polymorphisms have been linked to changes in disease onset and activity, 66,67 suggesting that this pathway contributes to the recruitment of cDCs to the inflamed CNS of MS patients.…”

Section: Phenotype and Function In Msmentioning

confidence: 99%

Role and therapeutic value of dendritic cells in central nervous system autoimmunity

2014

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Dendritic cells (DCs) are professional antigen-presenting cells that control the generation of adaptive immunity. Consequently, DCs have a central role in the induction of protective immunity to pathogens and also in the pathogenic immune response responsible for the development and progression of autoimmune disorders. Thus the study of the molecular pathways that control DC development and function is likely to result in new strategies for the therapeutic manipulation of the immune response. In this review, we discuss the role and therapeutic value of DCs in autoimmune diseases, with a special focus on multiple sclerosis. Cell Death and Differentiation (2015) 22, 215-224; doi:10.1038/cdd.2014; published online 29 August 2014 FactsDendritic cells (DCs) control central and peripheral tolerance through their effects on effector and regulatory T cells. Specific signaling pathways regulate the ability of different DC populations to promote effector and regulatory T-cell responses. Abnormalities in DC numbers, recruitment and function contribute to the pathology of multiple sclerosis (MS) and can be partially overcome by the use of disease-modifying therapies and the targeting of specific molecular pathways. Nanotechnology provides new tools for the modulation of DC activity in vivo and the therapeutic induction of antigenspecific tolerance in immune-mediated disorders. Open QuestionsAlthough DC populations that promote the development of forkhead box P3-positive (FoxP3 þ ) regulatory T cells (Tregs) have been identified, it is not yet clear whether these populations constitute separate tolerogenic DC lineages or represent alternative activation or maturation states of other DC populations. What are the different molecular pathways that control the DC's ability to prime effector or tolerogenic T-cell responses?There is an unmet clinical need for the development of methods for the efficient and consistent generation of tolerogenic DCs in vitro and in vivo that can be implemented in large-scale clinical setups.Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that control the activation and polarization of T cells into specific lineages and, consequently, the generation of antigen-specific antibody and T-cell responses. 1 In the context of an infectious challenge, the induction of pathogenspecific immune responses provides protective immunity to fight the infection. However, in the context of autoimmune diseases DCs regulate the balance between pathogenic and regulatory immune mechanisms, controlling disease onset and progression. Thus, DCs have a central role in the control of the adaptive immune response to pathogens and selftissues and therefore constitute potential targets for the therapeutic modulation of the immune response. In this review, we discus the role of DCs in autoimmune diseases, with a special emphasis on their role in the modulation of central nervous system (CNS) inflammation in MS. Received 12.6.14; accepted 23.6.14; Edited by H-U Simon; published online 29.8.14 Abbreviations: A...

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