scholarly journals 1-alpha,25-Dihydroxyvitamin D3 (1,25(OH)(2)D(3)) hampers the maturation of fully active immature dendritic cells from monocytes

2001 ◽  
pp. 351-357 ◽  
Author(s):  
MO Canning ◽  
K Grotenhuis ◽  
H de Wit ◽  
C Ruwhof ◽  
HA Drexhage
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Transforming Growth Factor ◽  
Human Peripheral Blood ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cell Mediated Immunity ◽  
Tgf Beta ◽  
Gm Csf ◽  
Immature Dendritic Cells ◽  
Hla Dr

OBJECTIVE: To study the effects of the active metabolite of vitamin D(3), 1,25(OH)(2)D(3), an immunomodulatory hormone, on the generation of so-called immature dendritic cells (iDCs) generated from monocytes (Mo-iDCs). DESIGN AND METHODS: Human peripheral blood monocytes were cultured to iDCs in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 for 1 week, with or without the extra addition of 10(-8) M 1,25(OH)(2)D(3) to the culture. Their phenotypes (CD14, CD1a, CD83, HLA-DR, CD80, CD86 and CD40 expression) were examined by fluorescence-activated cell sorting, and their T-cell stimulatory potential was investigated in allogeneic mixed lymphocyte reaction (allo-MLR). Additionally, their in vitro production of IL-10, IL-12 and transforming growth factor beta (TGF-beta) were examined by using the enzyme-linked immunosorbent assay. RESULTS: When 1,25(OH)(2)D(3) was added to monocytes in culture with GM-CSF and IL-4, it hampered the maturation of Mo-iDCs. First, the phenotype of the 1,25(OH)(2)D(3)-differentiated DCs was affected, there being impaired downregulation of the monocytic marker CD14 and impaired upregulation of the markers CD1a, CD83, HLA-DR, CD80 and CD40. CD86 was expressed on more 1,25(OH)(2)D(3)-differentiated DCs. Secondly, the T-cell stimulatory capability of 1,25(OH)(2)D(3)-differentiated DCs was upregulated relative to the original monocytes to a lesser degree than DCs differentiated without 1,25(OH)(2)D(3) when tested in an allo-MLR. With regard to the production of cytokines, Staphylococcus aureus cowan 1 strain (SAC)-induced IL-10 production, although not enhanced, remained high in 1,25(OH)(2)D(3)-differentiated DCs, but was strongly downregulated in DCs generated in the absence of 1,25(OH)(2)D(3). SAC/interferon-gamma-induced IL-12 production was clearly upregulated in both types of DC relative to those of the original monocytes, and TGF-beta production was downregulated. CONCLUSION: Our data confirm earlier reports showing that 1,25(OH)(2)D(3) hampers the maturation of fully active immunostimulatory major histocompatibility complex (MHC) class II+, CD1a+, CD80+ DCs from monocytes. Our data supplement the data from other reports by showing that the expression of CD86 was upregulated in 1,25(OH)(2)D(3)-differentiated DCs, whilst the capacity for IL-10 production remained high. Collectively, these data are in line with earlier descriptions of suppressive activities of this steroid-like hormone with respect to the stimulation of cell-mediated immunity.

Ketamine Affects In Vitro Differentiation of Monocyte into Immature Dendritic Cells

2015 ◽  
Vol 123 (3) ◽  
pp. 628-641 ◽  
Author(s):  
Krzysztof Laudanski ◽  
Meng Qing ◽  
Hanna Oszkiel ◽  
Mateusz Zawadka ◽  
Natalia Lapko ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Transforming Growth Factor ◽  
Neutralizing Antibody ◽  
Transforming Growth Factor Β ◽  
Nmda Receptor Antagonist ◽  
Interleukin 4 ◽  
Mk 801 ◽  
Gm Csf ◽  
Immature Dendritic Cells

Abstract Background: Monocytes (MOs) have the unique ability to differentiate into immature dendritic cells (iDCs) (MO→iDC) under the influence of interleukin-4 and granulocyte–monocyte colony-stimulating factor (IL-4&GM-CSF). In this study, the authors investigated the influence of ketamine on the process of MO→iDC. Methods: iDCs were cultured from MO obtained from 36 subjects in the presence of IL-4 and GM-CSF and ketamine at 100, 10, and 1 μg/ml for 5 days. In some of the experiments, the authors used nonspecific N-methyl-d-aspartate (NMDA) receptor antagonist MK-801, NMDA, or a neutralizing antibody for transforming growth factor β (TGFβ). The expression of surface markers and functional assays were used to assess the effect of ketamine on IL-4&GM-CSF-stimulated MO. IL-4&GM-CSF-stimulated MO’s supernatants were assessed for cytokine levels. Results: Ketamine at 10 μg/ml, and higher concentrations, diminished the expression of CD1a on IL-4&GM-CSF-stimulated MO and retarded both their ability to process DQ ovalbumin and mixed lymphocyte reaction stimulation. The addition of ketamine to IL-4&GM-CSF-differentiated MO resulted in the persistent expression of CD14 and unchanged expression of CD86 and CD206. The phagocytic abilities of IL-4&GM-CSF-differentiated MO were not changed by ketamine. MK-801, a nonselective NMDA agonist, mimicked ketamine’s effect on MO→iDC differentiation. Adding exogenous NMDA to IL-4&GM-CSF-stimulated MO in the presence of ketamine partially restored the level of CD1a+. TGFβ was elevated in supernatants of IL-4&GM-CSF-stimulated MO in the presence of ketamine. Adding neutralizing TGFβ antibody or TGFβR1 blocker (SB431542) resulted in the full recovery of MO→iDC, despite the presence of ketamine. Conclusions: Ketamine diminishes the process of MO→iDC in vitro. This is mediated via NMDA-dependent mechanisms and TGFβ.

Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells

Blood ◽  
2005 ◽  
Vol 105 (3) ◽  
pp. 1162-1169 ◽  
Author(s):  
Megan K. Levings ◽  
Silvia Gregori ◽  
Eleonora Tresoldi ◽  
Sabrina Cazzaniga ◽  
Chiara Bonini ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Transforming Growth Factor ◽  
Cellular Therapy ◽  
Transforming Growth Factor Β ◽  
Interleukin 10 ◽  
Peripheral Tolerance ◽  
Immature Dendritic Cells ◽  
Tr1 Cells

Abstract Dendritic cells (DCs) are specialized antigen-presenting cells that monitor the antigenic environment and activate naive T cells. The role of DCs is not only to sense danger but also to tolerize the immune system to antigens encountered in the absence of maturation/inflammatory stimuli. Indeed, if a naive T cell encounters its antigen on immature DCs (iDCs), it may differentiate into a T-regulatory (Tr) rather than a T-effector cell. However, little is known about the mechanisms by which iDCs differentiate Tr cells. We developed a standardized and highly reproducible protocol to differentiate Tr cells by repetitive exposure of naive peripheral blood CD4+ T cells to allogeneic iDCs. The resultant Tr cells are phenotypically and functionally identical to type 1 Tr (Tr1) cells because their generation requires production of IL-10 by iDCs, and they suppress T-cell responses through an interleukin-10 (IL-10)– and a transforming growth factor β (TGF-β)–dependent mechanism. In addition, Tr1 cells induced by iDCs do not require the presence of CD4+CD25+ Tr cells for their generation, nor do they express high constitutive levels of CD25 or the transcription factor FoxP3. Thus, iDCs can drive the differentiation of Tr1 cells and can be used to generate large numbers of alloantigen-specific Tr1 cells for clinical use as a cellular therapy to restore peripheral tolerance.

Cotransfection with IL-10 and TGF-β1 into immature dendritic cells enhances immune tolerance in a rat liver transplantation model

2014 ◽  
Vol 306 (7) ◽  
pp. G575-G581 ◽  
Author(s):  
Lihong Chen ◽  
Lin Zheng ◽  
Wubing He ◽  
Minglian Qiu ◽  
Lingyun Gao ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Dendritic Cells ◽  
T Cell ◽  
Immune Tolerance ◽  
Transforming Growth Factor ◽  
Liver Graft ◽  
Promising Alternative ◽  
Immature Dendritic Cells ◽  
Tgf Β1 ◽  
Transplantation Model

Dendritic cells transfected with interleukin (IL)-10 and transforming growth factor-β1 (TGF-β1) enhance T cell immunity and tolerance. However, no quantitative studies have investigated the suppressive functions of immature dendritic cells (imDC) cotransfected with IL-10 and TGF-β1. The effects of imDC cotransfected with IL-10 and TGF-β1 (IL-10-TGF-β1-imDC) on immune tolerance induction in a rat transplantation model were investigated. In addition, effects of IL-10-TGF-β1-imDC relative to IL-10-transfected imDC (IL-10-imDC) and TGF-β1-transfected imDC (TGF-β1-imDC) were compared. The infusion of IL-10-TGF-β1-imDC into recipients prolonged liver graft survival, which was sustained for >90 days. IL-12 serum levels decreased, whereas alanine transaminase and total bilirubin slightly increased in rats infused with IL-10-TGF-β1-imDC compared with the IL-10-imDC and TGF-β1-imDC groups. Furthermore, a higher percentage of terminal transferase-mediated UTP nick end-labeling-positive cells was observed, and histological analysis of the allografts indicated a rejection activity index of mild acute rejection. Our results suggest infusion of IL-10 and TGF-β1 cotransfected imDC induces alloantigen-specific T cell hyporesponsiveness, inhibits antigen-specific immunological responses to liver allografts, prolongs liver allograft survival, and enhances the immune tolerance. This approach may provide a promising alternative for enhancing donor-specific tolerance during liver transplantation.

scholarly journals A distinct pattern of cytokine gene expression by human CD83+ blood dendritic cells

Blood ◽  
1995 ◽  
Vol 86 (9) ◽  
pp. 3295-3301 ◽  
Author(s):  
LJ Zhou ◽  
TF Tedder
Keyword(s):  
Gene Expression ◽  
Dendritic Cells ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Distinct Pattern ◽  
Cytokine Gene Expression ◽  
Cytokine Gene ◽  
Tgf Beta ◽  
Necrosis Factor Alpha ◽  
Gm Csf

Dendritic cells are the most potent antigen-presenting cells of the immune system. Although dendritic cells are likely to secrete selective cytokines that facilitate antigen presentation, the difficulty in isolating pure dendritic cells in sufficient numbers has made assessment of this function imprecise. In this study, pure populations of CD83+ human blood dendritic cells were isolated by previously established enrichment procedures and subsequent cell sorting. Cytokine gene expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR) amplification of mRNA. Resting CD83+ dendritic cells expressed interleukin-6 (IL-6), IL-8, IL-10, tumor necrosis factor- alpha (TNF-alpha), and transforming growth factor-beta 1 (TGF-beta 1) mRNA, while activation of cells with phorbol myristate acetate induced IL-1 alpha and beta, IL-9, TNF-beta, interferon-gamma, granulocyte- macrophage colony-stimulating factor (GM-CSF), M-CSF, and G-CSF mRNA expression. Resting CD83+ cells also expressed the Rantes, MCP-1, MIP-1 alpha, and MIP-1 beta chemokines, with 1–309 expression induced upon activation. Resting and activated CD83+ dendritic cells also expressed receptors for IL-2 (CD25), TGF-beta 1 and -beta 3, and GM-CSF as determined by indirect immunofluorescence staining. These results indicate that dendritic cells have the ability to produce a variety of soluble factors which are likely to contribute substantially to the potent allostimulatory activity of these cells.

scholarly journals Interleukin 15 Skews Monocyte Differentiation into Dendritic Cells with Features of Langerhans Cells

2001 ◽  
Vol 194 (7) ◽  
pp. 1013-1020 ◽  
Author(s):  
Mansour Mohamadzadeh ◽  
Frederic Berard ◽  
Gregory Essert ◽  
Cecile Chalouni ◽  
Bali Pulendran ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Langerhans Cells ◽  
Monocyte Differentiation ◽  
Gm Csf ◽  
Inflammatory Protein ◽  
Immature Dendritic Cells ◽  
Hla Dr ◽  
Bona Fide ◽  
Macrophage Colony ◽  
Antigen Presenting

Langerhans cells (LCs) represent a subset of immature dendritic cells (DCs) specifically localized in the epidermis and other mucosal epithelia. As surrounding keratinocytes can produce interleukin (IL)-15, a cytokine that utilizes IL-2Rγ chain, we analyzed whether IL-15 could skew monocyte differentiation into LCs. Monocytes cultured for 6 d with granulocyte/macrophage colony-stimulating factor (GM-CSF) and IL-15 differentiate into CD1a+HLA-DR+CD14−DCs (IL15-DCs). Agents such as lipopolysaccharide (LPS), tumor necrosis factor (TNF)α, and CD40L induce maturation of IL15-DCs to CD83+, DC-LAMP+ cells. IL15-DCs are potent antigen-presenting cells able to induce the primary (mixed lymphocyte reaction [MLR]) and secondary (recall responses to flu-matrix peptide) immune responses. As opposed to cultures made with GM-CSF/IL-4 (IL4-DCs), a proportion of IL15-DCs expresses LC markers: E-Cadherin, Langerin, and CC chemokine receptor (CCR)6. Accordingly, IL15-DCs, but not IL4-DCs, migrate in response to macrophage inflammatory protein (MIP)-3α/CCL20. However, IL15-DCs cannot be qualified as “genuine” Langerhans cells because, despite the presence of the 43-kD Langerin, they do not express bona fide Birbeck granules. Thus, our results demonstrate a novel pathway in monocyte differentiation into dendritic cells.

Osteopontin functionally activates dendritic cells and induces their differentiation toward a Th1-polarizing phenotype

Blood ◽  
2005 ◽  
Vol 106 (3) ◽  
pp. 946-955 ◽  
Author(s):  
Andreas C. Renkl ◽  
Julia Wussler ◽  
Thomas Ahrens ◽  
Käthe Thoma ◽  
Shigeyuki Kon ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Interferon Γ ◽  
Interleukin 12 ◽  
Cell Mediated Immunity ◽  
T Helper 1 ◽  
Hla Dr ◽  
Th1 Cytokine ◽  
Factor Α

AbstractOsteopontin (OPN) has been shown to have T helper 1 (Th1) cytokine functions in cell-mediated immunity. Deficiency of OPN is linked to a reduced Th1 immune response in autoimmunity, infectious disease, and delayed-type allergy. Dendritic cells (DCs) are central for the induction of T-cell–mediated immunity, when initially flexible DCs are instructed by priming signals and tissue-derived factors to adopt Th1, Th2, or regulatory T-cell–inducing phenotypes. Although OPN influences the cytokine secretion of T cells and macrophages, its effects on DC polarization remain an important missing link in the understanding of OPN functions in Th1 immunity. Here we demonstrate that OPN promotes the emigration of human DCs from the epidermis and functionally activates myeloid-type DCs, augmenting their expression of HLA-DR, costimulatory, and adhesion molecules. OPN induces their Th1-promoting tumor necrosis factor α (TNF-α) and interleukin-12 (IL-12) secretion, and enhances their allostimulatory capacity. In mixed lymphocyte reactions (MLRs), OPN stimulates IL-12 secretion by DCs, inducing elevated interferon-γ (IFN-γ) production by T cells. Naive Th cells stimulated by OPN-activated DCs show a Th1-polarized cytokine production. Our findings identify OPN as an important tissue-derived factor that DCs encounter when traveling from peripheral sites of activation to secondary lymphatic organs, which induces DC maturation toward a Th1-promoting phenotype.

scholarly journals Transactivation of the transforming growth factor beta 1 (TGF-beta 1) gene by human T lymphotropic virus type 1 tax: a potential mechanism for the increased production of TGF-beta 1 in adult T cell leukemia.

1990 ◽  
Vol 172 (1) ◽  
pp. 121-129 ◽  
Author(s):  
S J Kim ◽  
J H Kehrl ◽  
J Burton ◽  
C L Tendler ◽  
K T Jeang ◽  
...  
Keyword(s):  
T Cell ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Leukemic Cells ◽  
Tgf Beta ◽  
Cell Leukemia ◽  
T Lymphotropic Virus ◽  
Adult T Cell Leukemia ◽  
Growth Factor Beta

We examined the effect of the human T lymphotropic virus type 1 (HTLV-I) Tax gene product on the human transforming growth factor beta 1 (TGF-beta 1) promoter. Transfection of deleted constructs of the TGF-beta 1 promoter revealed regions homologous with AP-1 binding sites that were required for Tax-induced transactivation of the TGF-beta 1 promoter. In addition, we examined the expression and secretion of TGF-beta in fresh leukemic cells isolated from patients with adult T cell leukemia (ATL) and in HTLV-1-infected T cell lines. We report that fresh leukemic cells from ATL patients constitutively produce high levels of TGF-beta 1 mRNA and secrete TGF-beta 1 but not TGF-beta 2 into the culture medium. In addition, long-term ATL cell lines expressed significant amounts of TGF-beta 1 mRNA as well as detectable levels of TGF-beta 1 protein. These results suggest a role for Tax in the upregulation of TGF-beta 1 in HTLV-I-infected cells.

scholarly journals Transforming growth factor beta suppresses human immunodeficiency virus expression and replication in infected cells of the monocyte/macrophage lineage.

1991 ◽  
Vol 173 (3) ◽  
pp. 589-597 ◽  
Author(s):  
G Poli ◽  
A L Kinter ◽  
J S Justement ◽  
P Bressler ◽  
J H Kehrl ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Growth Factor ◽  
Cell Line ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Tgf Beta ◽  
Immunodeficiency Virus ◽  
Growth Factor Beta

The pleiotropic immunoregulatory cytokine transforming growth factor beta (TGF-beta) potently suppresses production of the human immunodeficiency virus (HIV), the causative agent of the acquired immunodeficiency syndrome, in the chronically infected promonocytic cell line U1. TGF-beta significantly (50-90%) inhibited HIV reverse transcriptase production and synthesis of viral proteins in U1 cells stimulated with phorbol myristate acetate (PMA) or interleukin 6 (IL-6). Furthermore, TGF-beta suppressed PMA induction of HIV transcription in U1 cells. In contrast, TGF-beta did not significantly affect the expression of HIV induced by tumor necrosis factor alpha (TNF-alpha). These suppressive effects were not mediated via the induction of interferon alpha (IFN-alpha). TGF-beta also suppressed HIV replication in primary monocyte-derived macrophages infected in vitro, both in the absence of exogenous cytokines and in IL-6-stimulated cultures. In contrast, no significant effects of TGF-beta were observed in either a chronically infected T cell line (ACH-2) or in primary T cell blasts infected in vitro. Therefore, TGF-beta may play a potentially important role as a negative regulator of HIV expression in infected monocytes or tissue macrophages in infected individuals.

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