Effect of interleukin‐10 on dendritic cell maturation and function

Smedt, Thibaut De; Mechelen, Marcelle Van; Becker, Geneviève De; Urbain, Jacques; Léo, Oberdan; Moser, Muriel

doi:10.1002/eji.1830270526

Cited by 495 publications

(349 citation statements)

References 46 publications

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“…In particular, injection of splenic DCs has been shown to induce the activation of T cells that secrete a large array of cytokines 3 17. Because DCs are the APCs of the primary immune response, we analyzed the adjuvant function of DCs purified from control and μMT mice.…”

Section: Resultsmentioning

confidence: 99%

“…Although we do not have direct evidence, several features suggest that IL-10 may be involved in this immunoregulatory process: splenocytes from μMT mice express reduced levels of IL-10 mRNA than wild-type animals; DCs from IL-10 knockout mice display properties similar to DCs from μMT mice, i.e., they have lost the capacity to induce the development of IL-4–secreting cells; treatment of DCs from μMT mice with IL-10 restored the generation of IL-4–producing cells in vivo; and numerous reports have shown that IL-10 inhibits the production of IL-12 heterodimer by DCs in vitro and in vivo 3 10. Collectively, these observations suggest that the level of IL-12 released by DCs is regulated by B lymphocytes, presumably via the production of IL-10.…”

Section: Discussionmentioning

confidence: 99%

“…The capacity of DCs to direct the development of selected Th populations has been shown to be modulated by pathogens, cytokines, and other environmental factors 2. In particular, we have shown that DCs may induce the development of Th0 (or Th1 and Th2) lymphocytes in a neutral environment, and the differentiation of a polarized Th1 or Th2 population in the presence of IL-12 or IL-10, respectively 3.…”

Section: Introductionmentioning

confidence: 87%

“…Proliferation was measured as thymidine incorporation during the last 16 h of a 3-d culture. Culture supernatants were assayed for IL-2 after 24 h of incubation, for IL-4 after 48 h, for IFN-γ after 72 h, and IL-5 and IL-10 after 96 h. IL-2 and IFN-γ were measured as previously described 3. IL-4, IL-5, and IL-10 were quantified by two-site ELISA from PharMingen.…”

Section: Methodsmentioning

confidence: 99%

“…The supernatants were assayed for IL-12 p40 after 48 h using a two-site ELISA 3. IL-12 p70 production was monitored on 72 h supernatants by a bioassay based on the ability of IL-12 to induce IFN-γ production by spleen cells.…”

Section: Methodsmentioning

confidence: 99%

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B Lymphocytes Regulate Dendritic Cell (Dc) Function in Vivo

Moulin

Andris

Thielemans

et al. 2000

The Journal of Experimental Medicine

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235

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Increasing evidence indicates that dendritic cells (DCs) are the antigen-presenting cells of the primary immune response. However, several reports suggest that B lymphocytes could be required for optimal T cell sensitization. We compared the immune responses of wild-type and B cell-deficient (μMT) mice, induced by antigen emulsified in adjuvant or pulsed on splenic dendritic cells. Our data show that lymph node cells from both control and μMT animals were primed, but each released distinct cytokine profiles. Lymph node T cells from control animals secreted interferon (IFN)-γ, interleukin (IL)-2, and IL-4, whereas those from μMT mice produced IFN-γ and IL-2 but no IL-4. To test whether B cells may influence the T helper cell type 1 (Th1)/Th2 balance by affecting the function of DCs, we immunized mice by transferring antigen-pulsed DCs from wild-type or mutant mice. Injection of control DCs induced the secretion of IL-4, IFN-γ, and IL-2, whereas administration of DCs from μMT animals failed to sensitize cells to produce IL-4. Analysis of IL-12 production revealed that DCs from μMT mice produce higher levels of IL-12p70 than do DCs from wild-type animals. These data suggest that B lymphocytes regulate the capacity of DCs to promote IL-4 secretion, possibly by downregulating their secretion of IL-12, thereby favoring the induction of a nonpolarized immune response.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 87%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

B Lymphocytes Regulate Dendritic Cell (Dc) Function in Vivo

Moulin

Andris

Thielemans

et al. 2000

The Journal of Experimental Medicine

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235

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IL-10 prevents the differentiation of monocytes to dendritic cells but promotes their maturation to macrophages

Allavena

Piemonti

Longoni³

et al. 1998

Eur. J. Immunol.

431

246

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Human monocytes cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-13 for 7 days differentiate into cells with the morphology and function of dend-ritic cells (DC). We have investigated the effect of IL-10 on this differentiation pathway. In the presence of IL-10 cells did not develop DC morphology, did not express CD1a and had lower levels of MHC class II. IL-10 promoted the differentiation of large cells with the morphology , cytochemistry and membrane phenotype of macrophages, including staining for nonspecific esterase and high levels of CD14, CD16 and CD68. The effect of IL-10 was dose dependent and was best appreciated when the cytokine was added at the initiation of the culture, as addition on day 3 was less inhibitory. When added to already differentiated DC on day 6, IL-10 caused only a modest reduction of MHC class II and CD1a expression, and no acquisition of the macrophage markers CD14, CD16 and CD68. Prolonged incubation up to 5 days with IL-10 did not induce a shift of differentiated DC to macrophages. On the other hand, the macrophages obtained by culturing for 7 days with GM-CSF+IL-13+IL-10 did not shift to DC upon removal of IL-10 for up to 3 days. Thus, the effect of IL-10 on monocyte differentiation , occurs only at the precursor level and confers an irreversible phenotype. From a functional point of view, cells cultured in the presence of IL-10 were poor stimulators of allogeneic cord blood T cells in mixed lymphocyte reaction (MLR) and presented tetanus toxin (TT) to specific T cell lines with much less efficiency than control DC. In contrast, IL-10-cultured DC showed 7 times greater endocytosis of FITC-dextran. This increased endocyto-sis was mostly mediated via the mannose receptor, as demonstrated by blocking with unla-beled mannose. In conclusion, IL-10 inhibits DC differentiation from monocytes and, in a substantial proportion of the cells, promotes the differentiation to mature macrophages. Intriguingly, IL-10 inhibits antigen presentation while it stimulates endocytic activity.

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Th1 cells induce and Th2 inhibit antigen-dependent IL-12 secretion by dendritic cells

1998

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Dendritic cells are the most relevant antigen-presenting cells (APC) for presentation of antigens administered in adjuvant to CD4 + T cells. Upon interaction with antigen-specific T cells, dendritic cells (DC) expressing appropriate peptide-MHC class II complexes secrete IL-12, a cytokine that drives Th1 cell development. To analyze the T cell-mediated regulation of IL-12 secretion by DC, we have examined their capacity to secrete IL-12 in response to stimulation by antigen-specific Th1 and Th2 DO11.10 TCR-transgenic cells. These cells do not differ either in TCR clonotype or CD40 ligand (CD40L) expression. Interaction with antigenspecific Th1, but not Th2 cells, induces IL-12 p40 and p75 secretion by DC. The induction of IL-12 production by Th1 cells does not depend on their IFN-+ secretion, but requires direct cell-cell contact mediated by peptide/MHC class II-TCR and CD40-CD40L interactions. Th2 cells not only fail to induce IL-12 secretion, but they inhibit its induction by Th1 cells. Unlike stimulation by Th1, inhibition of IL-12 production by Th2 cells is mediated by soluble molecules, as demonstrated by transwell cultures. Among Th2-derived cytokines, IL-10, but not IL-4 inhibit Th1-driven IL-12 secretion. IL-10 produced by Th2 cells appears to be solely responsible for the inhibition of Th1-induced IL-12 secretion, but it does not account for the failure of Th2 cells to induce IL-12 production by DC. Collectively, these results demonstrate that Th1 cells up-regulate IL-12 production by DC via IFN-+ -independent cognate interaction, whereas this is inhibited by Th2-derived IL-10. The inhibition of Th1-induced IL-12 production by Th2 cells with the same antigen specificity represents a novel mechanism driving the polarization of CD4 + T cell responses.

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Effect of interleukin‐10 on dendritic cell maturation and function

Cited by 495 publications

References 46 publications

B Lymphocytes Regulate Dendritic Cell (Dc) Function in Vivo

B Lymphocytes Regulate Dendritic Cell (Dc) Function in Vivo

IL-10 prevents the differentiation of monocytes to dendritic cells but promotes their maturation to macrophages

Th1 cells induce and Th2 inhibit antigen-dependent IL-12 secretion by dendritic cells

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