Dendritic cells in inflammatory joint disease

Knight, Stella C.

doi:10.1007/978-94-009-1293-9_4

Cited by 7 publications

(3 citation statements)

References 68 publications

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“…The effects of αIL-6 are in marked contrast to the inhibitory effects of αTNF Ab, which selectively downregulates mono-DC hematopoiesis while sparing the development of granulocytes [5]. Because of the important role of granulocytes in innate immunity, αTNF may be more useful than αIL-6 in developing therapeutic strategies designed to downregulate the DC pathway in autoimmune diseases characterized by an excess of DCs, such as rheumatoid arthritis [26,27]. In other pathological situations characterized by deficiencies in DC development such as the ORL47 myelodendritic leukemia [13], it may be useful to promote the terminal maturation of DCs with exogenous IL-6 + GM-CSF + TNF + SCF.…”

Section: Fig 3 the Effect Of Rb Polyclonal αIl-6 Ab (10 µG/ml) Addementioning

confidence: 99%

Endogenously Produced Interleukin 6 is an Accessory Cytokine for Dendritic Cell Hematopoiesis

1996

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Abstract. The aim of this study was to investigate the role of interleukin 6 (IL-6) in normal dendritic cell (DC) hematopoiesis. We used an enzyme-linked immunosorbent assay to quantitate IL-6 levels in CD34 + progenitor cell cultures favoring monocyte (mono) development versus those supporting mono-DC growth, and studied the neutralizing effects of αIL-6 antibody on DC hematopoiesis. IL-6 levels in mono cultures (GM-CSF alone) were detected by day 4 and remained constant (~100 pg/ml) for 18 days. In mono-DC cultures, higher IL-6 levels correlated with DC content and development. Shortterm mono-DC cultures initiated with GM-CSF + tumor necrosis factor (TNF) + stem cell factor (SCF) exhibited increases in IL-6 levels until day 11 (peak DC growth). By day 18, the levels had declined and cells expressing typical DC features were no longer present. Long-term mono-DC cultures sustained with GM-CSF + TNF + SCF contained the highest IL-6 levels (671 pg/ml) on day 11. In these cultures, DCs and higher IL-6 levels persisted beyond 18 days. Anti-IL-6 profoundly inhibited cell proliferation associated with DC hematopoiesis when added on days 0, 2 and 5 to GM-CSF + TNF + SCF cultures, indicating that various stages of mono-DC development rely on IL-6. There was no reduction in the T cell response when αIL-6 was added to mixed leukocyte reaction cultures containing mature DCs as stimulators. Thus, αIL-6 appears to downregulate developmental processes associated with optimal mono-DC growth, but not the effector functions of mature DCs.These studies substantiate the importance of IL-6 as a secondary cytokine during DC development and provide insight into another control point in the DC pathway.

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Section: Fig 3 the Effect Of Rb Polyclonal αIl-6 Ab (10 µG/ml) Addementioning

confidence: 99%

Endogenously Produced Interleukin 6 is an Accessory Cytokine for Dendritic Cell Hematopoiesis

1996

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“…These are distinct from the follicular dendritic cells of the B-dependent areas which arise in situ from fibroblastic reticulum cells [24]. In patients with inflammatory arthritis, however, DC are increased in the synovial membranes and fluids compared with noninflammatory tissues [25][26][27][28][29][30][31]. DC in the joints are distinct from fibroblasts which have been described as 'dendritic' in morphology [28].…”

Section: The Autologous Mixed Lymphocyte Reaction and Dendritic Cellsmentioning

confidence: 99%

“…The evidence for involvement of DC in the development of inflammatory arthritis in humans is circumstantial. The dendritic cells are present in increased numbers in the synovium and in the synovial fluid [23][24][25][26][27][28]. In some patients, DC from synovial fluid can produce high levels of stimulation of syngeneic lympho-cytes from peripheral blood [31] supporting the idea that dendritic cells with antigen may be providing a continuing stimulus to the lymphocytes within the joints.…”

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confidence: 99%

The Autologous Mixed Lymphocyte Reaction and Dendritic Cells

Knight¹

1987

Rheumatology

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TNF in combination with GM-CSF enhances the differentiation of neonatal cord blood stem cells into dendritic cells and macrophages

Santiago‐Schwarz

Belilos

Diamond

et al. 1992

Journal of Leukocyte Biology

234

130

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We describe dendritic cell progenitors within the CD34+ stem cell compartment in neonatal cord blood and identify growth factors contributing to their differentiation. Granulocyte-macrophage colony-stimulating factor (GM-CSF), although mainly promoting the growth and differentiation of monocyte-macrophages (mono-m psi s), also induced the differentiation of cells with the distinctive morphological features of dendritic cells (DCs). Tumor necrosis factor (TNF) in combination with GM-CSF promoted further growth of both cell types but most notably increased the DC content. In situ analysis revealed that the cells exhibiting DC morphology were positive for class II major histocompatibility complex antigens but were CD14 negative, did not exhibit nonspecific esterase activity, and were nonphagocytic. Moreover, the mixed leukocyte reaction stimulatory capacity of cultures with the higher DC content was greater. TNF, interleukin-1 (IL-1), IL-6, or platelet-derived growth factor (PDGF) was inactive in promoting stem cell proliferation or DC morphology. IL-1 or PDGF synergized with GM-CSF to increase mono-m psi-associated cell proliferation but did not increase the DC content. The development of a common DC-monocyte precursor was suggested by the presence of colony-forming unit-like clusters containing mono-m psi s and DCs and one sharp proliferative peak. The loss of DC morphology after 21 days, coupled with increases in mono-m psi-associated markers and a constant number of viable cells, further suggests that DC morphology may fluctuate in culture or is a transient feature acquired by certain cells of the mono-m psi lineage.

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Dendritic cells in inflammatory joint disease

Cited by 7 publications

References 68 publications

Endogenously Produced Interleukin 6 is an Accessory Cytokine for Dendritic Cell Hematopoiesis

Endogenously Produced Interleukin 6 is an Accessory Cytokine for Dendritic Cell Hematopoiesis

The Autologous Mixed Lymphocyte Reaction and Dendritic Cells

TNF in combination with GM-CSF enhances the differentiation of neonatal cord blood stem cells into dendritic cells and macrophages

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