Human dendritic cell responses to lipopolysaccharide and CD40 ligation are differentially regulated by interleukin‐10

Buelens, Christel; Verhasselt, Valérie; Groote, Donat De; Thielemans, Kris; Goldman, Michel; Willems, Fabienne

doi:10.1002/eji.1830270805

Cited by 181 publications

(110 citation statements)

References 31 publications

(6 reference statements)

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“…At the same time, mature DC remaining in tissues demonstrate normal levels of functional activity and functionally potent DC can be generated from progenitors in patients even with advanced stages of cancer (3-6, 8 -10). Tumor-derived factors dramatically affect DC differentiation in vitro (23)(24)(25)(26)(27). Decreased DC production was associated with accumulation of monocytes/macrophages and immature myeloid cells.…”

Section: Discussionmentioning

confidence: 99%

Increased Production of Immature Myeloid Cells in Cancer Patients: A Mechanism of Immunosuppression in Cancer

Almand

Clark

Nikitina

et al. 2001

The Journal of Immunology

1,190

966

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Defective dendritic cell (DC) function caused by abnormal differentiation of these cells is an important mechanism of tumor escape from immune system control. Previously, we have demonstrated that the number and function of DC were dramatically reduced in cancer patients. This effect was closely associated with accumulation of immature cells (ImC) in peripheral blood. In this study, we investigated the nature and functional role of those ImC. Using flow cytometry, electron microscopy, colony formation assays, and cell differentiation in the presence of different cell growth factors, we have determined that the population of ImC is composed of a small percentage (<2%) of hemopoietic progenitor cells, with all other cells being represented by MHC class I-positive myeloid cells. About one-third of ImC were immature macrophages and DC, and the remaining cells were immature myeloid cells at earlier stages of differentiation. These cells were differentiated into mature DC in the presence of 1 μM all-trans-retinoic acid. Removal of ImC from DC fractions completely restored the ability of the DC to stimulate allogeneic T cells. In two different experimental systems ImC inhibited Ag-specific T cell responses. Thus, immature myeloid cells generated in large numbers in cancer patients are able to directly inhibit Ag-specific T cell responses. This may represent a new mechanism of immune suppression in cancer and may suggest a new approach to cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Increased Production of Immature Myeloid Cells in Cancer Patients: A Mechanism of Immunosuppression in Cancer

Almand

Clark

Nikitina

et al. 2001

The Journal of Immunology

1,190

966

View full text Add to dashboard Cite

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“…inefficient APC [25,26]. This may result in an inefficient adaptive response against pyogenic bacteria, but augment the innate response against these microogranisms.…”

Section: Discussionmentioning

confidence: 99%

“…Multiple DC maturation factors, including TNF-a, IL-1b and LPS, are found in CSF in BM [23]. However, in meningitis, the CSF also contains IL-10, a potent DC-down-regulating factor [24], which prevents LPS-induced DC maturation [25] and converts DC into CD14 + macrophage-like cells [26]. In different neuroinflammatory diseases, these factors may have a different net effect on the behaviour of CSF DC which, in turn, may influence the character of the intrathecal immune response.…”

Section: Introductionmentioning

confidence: 99%

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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“…33 -35 It is also possible that TNF-a can be crucial for DC survival in cultures. 30,36 Apparently, DC are also able to produce TNF-a 35,37 and were even considered as a major source of TNF-a, in addition to macrophages. 38 Production of TNF-a by DC or addition of TNF-a to DC cultures greatly enhances numbers of DC and the level of their maturation as determined by the increased expression of surface molecules MHC class I and II, CD83, CD80 (B7-1), and CD86 (B7-2).…”

Section: Discussionmentioning

confidence: 99%

TNF-α protects dendritic cells from prostate cancer-induced apoptosis

Pirtskhalaishvili

Shurin

Esche

et al. 2001

Prostate Cancer Prostatic Dis

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We have recently shown that human prostate cancer (PCa) cells induced apoptotic death of the most potent antigen-presenting cells, dendritic cells (DC), which are responsible for the induction of specific antitumor immune responses. Here we have evaluated the effect of murine PCa cells RM-1 on the survival of immature and tumor necrosis factor-a (TNF-a)-stimulated mature DC. PCa cells and DC were co-incubated for 24 -48 h and DC apoptosis was assessed by morphologic criteria, Annexin V assay, and TUNEL staining. We have shown that co-incubation of RM-1 cells with DC is accompanied by an increased level of DC apoptosis, which was mediated by decreased expression of anti-apoptotic protein Bcl-2. Stimulation of DC maturation by TNF-a resulted in increased resistance of DC to PCa-induced apoptosis. In TNF-a treated mature DC, but not in immature DC, the expression of Bcl-2 was not blocked after exposure to RM-1-derived factors. Thus, these data suggest that TNF-a-induced maturation of DC increases their resistance to PCa induced apoptosis. This is likely to be due to the stabilizing of the expression of anti-apoptotic protein Bcl-2. The difference in the sensitivity of mature and immature DC to PCa-induced cell death should be considered during the design of DC-based clinical trials for PCa patients. Prostate Cancer and Prostatic Diseases (2001) 4, 221-227.

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Human dendritic cell responses to lipopolysaccharide and CD40 ligation are differentially regulated by interleukin‐10

Cited by 181 publications

References 31 publications

Increased Production of Immature Myeloid Cells in Cancer Patients: A Mechanism of Immunosuppression in Cancer

Increased Production of Immature Myeloid Cells in Cancer Patients: A Mechanism of Immunosuppression in Cancer

Cerebrospinal fluid affects phenotype and functions of myeloid dendritic cells

TNF-α protects dendritic cells from prostate cancer-induced apoptosis

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