scholarly journals Development of Interleukin-12-Producing Capacity throughout Childhood

2002 ◽  
Vol 70 (12) ◽  
pp. 6583-6588 ◽  
Author(s):  
John W. Upham ◽  
Peter T. Lee ◽  
Barbara J. Holt ◽  
Tricia Heaton ◽  
Susan L. Prescott ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Mononuclear Cells ◽  
Cell Function ◽  
Intrinsic Property ◽  
Interleukin 12 ◽  
Peripheral Blood Mononuclear ◽  
Hla Dr ◽  
Macrophage Colony ◽  
Synthetic Capacity ◽  
Th1 Immune Responses

ABSTRACT Increasing evidence indicates that the capacity to induce protective Th1 immune responses is impaired in early childhood, an observation that can be partially attributed to deficiencies in antigen-presenting-cell function. Synthesis of interleukin 12 (IL-12), a key Th1-trophic cytokine, is markedly reduced in the neonatal period, though there is a paucity of knowledge concerning the ontogeny of IL-12-synthetic capacity throughout the childhood years. Hence, we examined the production of bioactive IL-12 p70 by circulating mononuclear cells in a population of healthy individuals. As expected, the capacity to synthesize IL-12 p70 in response to either lipopolysaccharide or heat-killed Staphylococcus aureus was markedly impaired at birth, even after priming of cells with gamma interferon. Surprisingly however, IL-12 p70 synthesis by peripheral blood mononuclear cells from both 5- and 12-year-old children was still substantially below that seen in adults, and this did not appear to be related to excessive production of IL-10. In contrast, dendritic cells from adults and neonates, derived from monocytes with granulocyte-macrophage colony-stimulating factor and IL-4, synthesized equivalent amounts of IL-12 p70 in response to microbial stimulation. This indicates that the impaired capacity for IL-12 synthesis in childhood is not an intrinsic property of circulating mononuclear cells but rather can be readily overcome in response to appropriate maturational stimuli. Because IL-12 arose predominantly from circulating HLA-DR+ cells that lacked B-cell- and monocyte-specific markers, we propose that the slow maturation of IL-12-synthetic capacity in the childhood years can be attributed to deficiencies in the number and/or function of dendritic cells.

scholarly journals Endocarditis-Associated Oral Streptococci Promote Rapid Differentiation of Monocytes into Mature Dendritic Cells

2005 ◽  
Vol 73 (8) ◽  
pp. 5015-5021 ◽  
Author(s):  
Chin-Lo Hahn ◽  
Harvey A. Schenkein ◽  
John G. Tew
Keyword(s):  
Dendritic Cells ◽  
Mhc Class Ii ◽  
Mononuclear Cells ◽  
Oral Bacteria ◽  
Interleukin 12 ◽  
Oral Streptococci ◽  
Peripheral Blood Mononuclear ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Mixed Lymphocyte Reactions

ABSTRACT Endocarditis is frequently attributable to oral streptococci, but mechanisms of pathogenesis are not well understood, although monocytes appear to be important. High titers of interleukin-12 (IL-12) are produced by peripheral blood mononuclear cells (PBMC) after engaging Streptococcus mutans, but monocytes in developing endocardial vegetations tend to disappear rather than become macrophages. These data prompted the hypothesis that streptococcus-infected monocytes differentiate into short-lived IL-12-producing dendritic cells (DCs) rather than macrophages. PBMC from healthy subjects were stimulated with six isolates of oral streptococci, three nonstreptococcal oral bacteria, or IL-4 plus granulocyte-macrophage colony-stimulating factor, and the appearance of cells with markers typical of mature DCs (CD83+, CD86+, CD11c+, and CD14−) was monitored. Supernatant fluids from the PBMC cultures were harvested and IL-12 p70 levels were determined. S. mutans-stimulated monocytes were analyzed for their ability to elicit allogeneic mixed-lymphocyte reactions. All streptococci examined, except one strain of Streptococcus oralis (35037), rapidly induced up-regulation of CD83 and CD86 and a loss of CD14 in the CD11c+ monocyte population within 20 h. Induction of IL-12 was CD14 dependent and correlated with streptococcal isolates that promoted the DC phenotype. Major histocompatibility complex (MHC) class II expression was up-regulated by S. mutans, and these cells were short-lived and elicited potent allogeneic mixed-lymphocyte reactions typical of DCs. In summary, monocytes stimulated with endocarditis-associated oral streptococci rapidly exhibited the DC phenotype and functions. These data suggest that the initiation of bacterial endocarditis by oral streptococci may involve monocyte-to-DC differentiation, and this may help explain the low levels of macrophages in the site.

Expression of CCR6 and CD83 by cytokine-activated human neutrophils

Blood ◽  
2000 ◽  
Vol 96 (12) ◽  
pp. 3958-3963 ◽  
Author(s):  
Shigeo Yamashiro ◽  
Ji-Ming Wang ◽  
De Yang ◽  
Wang-Hua Gong ◽  
Hidenobu Kamohara ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Mononuclear Cells ◽  
Adaptive Immune Response ◽  
Immature Stage ◽  
Human Neutrophils ◽  
Peripheral Blood Mononuclear ◽  
Hla Dr ◽  
Tnf Α ◽  
Ifn Γ ◽  
Macrophage Colony

Polymorphonuclear leukocytes (PMNLs) are thought to be terminally differentiated, short-lived, and unable to actively synthesize new proteins or to interact with T cells. In the current study, it was found that PMNLs incubated with supernatants of phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PHA-sup) expressed high levels of CCR6 mRNA. Neutralization with IgG against several cytokines revealed that tumor necrosis factor (TNF)-α was largely responsible for the PHA-sup–induced CCR6 mRNA expression. Among recombinant cytokines, TNF-α induced high levels of CCR6 mRNA expression, whereas interferon (IFN)-γ induced low levels. The 2 cytokines together exhibited a considerable synergy. Cytokine-activated PMNLs expressed functional CCR6, as detected by the binding of sodium iodide I 125–labeled liver and activation-regulated chemokine (LARC) and dose-dependent migration toward LARC. The induction of CCR6 suggested that these cytokine-activated PMNLs have more similarities with dendritic cells (DCs) that express CCR6 in an immature stage. In fact, the activation of PMNLs with TNF-α and IFN-γ induced the expression of CD83, a dominant cell-surface marker of DCs. When PMNLs were activated with granulocyte macrophage–colony-stimulating factor, TNF-α, and IFN-γ, these cells expressed CD40 and HLA-DR in addition to CD83. Taken together, PMNLs, under appropriate conditions, can undergo a differentiation process characterized by the acquisition of new phenotypes and functions, and such differentiated PMNLs may play more active roles in the adaptive immune response.

Adenosine affects expression of membrane molecules, cytokine and chemokine release, and the T-cell stimulatory capacity of human dendritic cells

Blood ◽  
2003 ◽  
Vol 101 (10) ◽  
pp. 3985-3990 ◽  
Author(s):  
Elisabeth Panther ◽  
Silvia Corinti ◽  
Marco Idzko ◽  
Yared Herouy ◽  
Matthias Napp ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Mhc Class I ◽  
Class I ◽  
Interleukin 12 ◽  
T Helper 1 ◽  
Membrane Expression ◽  
Hla Dr ◽  
Factor Α ◽  
Human Dendritic Cells ◽  
Th1 Immune Responses

Abstract Dendritic cells (DCs) express functional purinergic type 1 receptors, but the effects of adenosine in these antigen-presenting cells have been only marginally investigated. Here, we further characterized the biologic activity of adenosine in immature DCs (iDCs) and lipopolysaccharide (LPS)–matured DCs (mDCs). Chronic stimulation with adenosine enhanced the macropinocytotic activity and the membrane expression of CD80, CD86, major histocompatibility complex (MHC) class I, and HLA-DR molecules on iDCs. Adenosine also increased LPS-induced CD54, CD80, MHC class I, and HLA-DR molecule expression in mDCs. In addition, adenosine dose-dependently inhibited tumor necrosis factor α and interleukin-12 (IL-12) release, whereas it enhanced the secretion of IL-10 from mDCs. The use of selective receptor agonists revealed that the modulation of the cytokine and cell-surface marker profile was due to activation of A2 adenosine receptor. Functionally, adenosine reduced the allostimulatory capacity of iDCs, but not of mDCs. More important, DCs matured in the presence of adenosine had a reduced capacity to induce T helper 1 (Th1) polarization of naive CD4+ T lymphocytes. Finally, adenosine augmented the release of the chemokine CCL17 and inhibited CXCL10 production by mDCs. In aggregate, the results provide initial evidence that adenosine diminishes the capacity of DCs to initiate and amplify Th1 immune responses.

Skewed X chromosomal inactivation impacts T regulatory cell function in systemic sclerosis

2010 ◽  
Vol 69 (12) ◽  
pp. 2213-2216 ◽  
Author(s):  
Jasper C A Broen ◽  
Ingrid L M Wolvers-Tettero ◽  
Lenny Geurts-van Bon ◽  
Madelon C Vonk ◽  
Marieke J H Coenen ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Systemic Sclerosis ◽  
T Regulatory Cells ◽  
Mononuclear Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Magnetic Bead ◽  
T Regulatory Cell ◽  
Myeloid Dendritic Cells ◽  
Peripheral Blood Mononuclear

ObjectivesTo investigate the role of X chromosomal inactivation (XCI) in systemic sclerosis (SSc) and its effects on forkhead box P3 (Foxp3) expression in T regulatory cells (Tregs).Methods217 women with SSc and 107 healthy women (controls) were included in the study. From these subjects, DNA was isolated from total peripheral blood mononuclear cells, plasmacytoid dendritic cells, T cells, B cells, myeloid dendritic cells and monocytes after magnetic bead separation. All samples were assessed for skewed XCI patterns with the Human Androgen Receptor Assay. The outcome was assessed by linear regression. CD4+CD25+ cells were then isolated and intracellular Foxp3 expression was assessed by flow cytometry.ResultsSkewing was not associated with increased age in patients with SSc, in contrast to the control population (r=0.45, p<0.0001). Taking this into account, a significantly higher frequency of skewed XCI was found in patients with SSc compared with controls (p=0.001). No difference in skewing was observed between the immune cell subsets. In addition, a higher concentration of Foxp3+ cells exhibiting a lower Foxp3 mean fluorescence intensity was found in the patients with SSc, with profound XCI skewing (both p<0.001) associated with less efficient suppressive activity (p=0.012).ConclusionsSkewed XCI plays a role in susceptibility to SSc, is not restricted and influences Foxp3 expression and the suppressive capacity of Tregs.

Immunotherapy, phase I study of immunotherapy with carcinoembryonic antigen peptide -pulsed, autologous human cultured dendritic cells in patients with advanced non-small cell lung cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 12517-12517
Author(s):  
B. Han ◽  
Z. Huan ◽  
F. Xiaohong ◽  
L. Rong ◽  
F. Guangli ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dendritic Cells ◽  
Carcinoembryonic Antigen ◽  
Mononuclear Cells ◽  
Dose Effect ◽  
Interleukin 4 ◽  
Advanced Lung Cancer ◽  
Peripheral Blood Mononuclear ◽  
Antigen Peptide ◽  
Macrophage Colony

12517 Background: To study toxicity tolerance and dose-effect relationship of carcinoembryuonic antigen peptide-pulsed dendritic cells in patients with advanced lung cancer. Methods: cells preparations enriched for autologous DCs were generated from the patients plastic adherent peripheral blood mononuclear cells in media supplemented with granulocyte macrophage colony -stimulating factor and interleukin-4. 37C0, 5%CO2 culture for 7–10. The DCs were loaded with carcinoembryonic antigen(CEA) in day 7, Groups of three to six patients received four weekly or biweekly i.v. infusions of the CAP-1-loaded DC in escalating dose levels of 1 × 106, 1 × 107, and 1 × 108 cells/dose. Patients with lung cancer received iv injections DCs. There were no toxicities directly referable to the treatments. Results: Total 22 patients with lung cancer received DCs immunotherapy. DCs infusion were 2.5×106-9.6×107,means 15.03×106. The early clinical trials suggest that vaccination with CEA vaccines is safe, producing few side-effects, and can lead to CEA-specific immunity. Conclusions: We conclude that it is feasible and safe to generate and administer large numbers of DCs loaded with CEA peptide to patients with lung cancer. No significant financial relationships to disclose.

Expression of CCR6 and CD83 by cytokine-activated human neutrophils

Blood ◽  
2000 ◽  
Vol 96 (12) ◽  
pp. 3958-3963 ◽  
Author(s):  
Shigeo Yamashiro ◽  
Ji-Ming Wang ◽  
De Yang ◽  
Wang-Hua Gong ◽  
Hidenobu Kamohara ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Mononuclear Cells ◽  
Adaptive Immune Response ◽  
Immature Stage ◽  
Human Neutrophils ◽  
Peripheral Blood Mononuclear ◽  
Hla Dr ◽  
Tnf Α ◽  
Ifn Γ ◽  
Macrophage Colony

Abstract Polymorphonuclear leukocytes (PMNLs) are thought to be terminally differentiated, short-lived, and unable to actively synthesize new proteins or to interact with T cells. In the current study, it was found that PMNLs incubated with supernatants of phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PHA-sup) expressed high levels of CCR6 mRNA. Neutralization with IgG against several cytokines revealed that tumor necrosis factor (TNF)-α was largely responsible for the PHA-sup–induced CCR6 mRNA expression. Among recombinant cytokines, TNF-α induced high levels of CCR6 mRNA expression, whereas interferon (IFN)-γ induced low levels. The 2 cytokines together exhibited a considerable synergy. Cytokine-activated PMNLs expressed functional CCR6, as detected by the binding of sodium iodide I 125–labeled liver and activation-regulated chemokine (LARC) and dose-dependent migration toward LARC. The induction of CCR6 suggested that these cytokine-activated PMNLs have more similarities with dendritic cells (DCs) that express CCR6 in an immature stage. In fact, the activation of PMNLs with TNF-α and IFN-γ induced the expression of CD83, a dominant cell-surface marker of DCs. When PMNLs were activated with granulocyte macrophage–colony-stimulating factor, TNF-α, and IFN-γ, these cells expressed CD40 and HLA-DR in addition to CD83. Taken together, PMNLs, under appropriate conditions, can undergo a differentiation process characterized by the acquisition of new phenotypes and functions, and such differentiated PMNLs may play more active roles in the adaptive immune response.

scholarly journals Dendritic Cell Profile Induced bySchistosoma mansoniAntigen in Cutaneous Leishmaniasis Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Diego Mota Lopes ◽  
Jamille Souza Fernandes ◽  
Thiago Marconi de Souza Cardoso ◽  
Aline Michele Barbosa Bafica ◽  
Sérgio Costa Oliveira ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Cutaneous Leishmaniasis ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Gm Csf ◽  
Surface Molecules ◽  
Hla Dr ◽  
Immune Mediated ◽  
Cell Profile

The inflammatory response in cutaneous leishmaniasis (CL), although responsible for controlling the infection, is associated with the pathogenesis of disease. Conversely, the immune response induced byS. mansoniantigens is able to prevent immune-mediated diseases. The aim of this study was to evaluate the potential of theS. mansoniSm29 antigen to change the profile of monocyte-derived dendritic cells (MoDCs) from subjects with cutaneous leishmaniasis (CL)in vitro. Monocytes derived from the peripheral blood mononuclear cells of twelve patients were cultured with GM-CSF and IL-4 for differentiation into dendritic cells and then stimulated with solubleLeishmaniaantigen (SLA) in the presence or absence of Sm29 antigen. The expression of surface molecules associated with maturation and activation (HLA-DR, CD40, CD83, CD80, and CD86), inflammation (IL-12, TNF), and downregulation (IL-10, IL-10R) was evaluated using flow cytometry. We observed that the frequencies of HLA-DR, CD83, CD80, and CD86 as well as of IL-10 and IL-10R on MoDCs were higher in cultures stimulated with Sm29, compared to the unstimulated cell cultures. Our results indicate that the Sm29 antigen is able to activate regulatory MoDCs in patients with cutaneous leishmaniasis. It might be useful to control the inflammatory process associated with this disease.

scholarly journals Feline immunodeficiency virus infection is enhanced by feline bone marrow-derived dendritic cells

2007 ◽  
Vol 88 (1) ◽  
pp. 251-258 ◽  
Author(s):  
F. J. U. M. van der Meer ◽  
N. M. P. Schuurman ◽  
H. F. Egberink
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Feline Immunodeficiency Virus ◽  
Mononuclear Cells ◽  
Interleukin 4 ◽  
Peripheral Blood Mononuclear ◽  
Feline Immunodeficiency Virus Infection ◽  
Immunodeficiency Virus ◽  
Macrophage Colony

In the pathogenesis of feline immunodeficiency virus (FIV) infection, feline dendritic cells (feDCs) are thought to play an important role. As with DCs in other species, feDCs are believed to transport virus particles to lymph nodes and transfer them to lymphocytes. Our investigation has focused on the ability of feDCs to influence the infection of syngeneic peripheral blood mononuclear cells (PBMCs) and allogeneic thymocytes. feDCs were derived from bone marrow mononuclear cells that were cultured under the influence of feline interleukin-4 and feline granulocyte–macrophage colony-stimulating factor. By using these feDCs in co-culture with resting PBMCs, an upregulation of FIV replication was shown. An enhancement of FIV infection was also detected when co-cultures of feDCs/feline thymocytes were infected. To obtain this enhancement, direct contact of the cells in the co-culture was necessary; transwell cultures showed that the involvement of only soluble factors produced by feDCs in this process is not likely. These feDCs were also able to induce the proliferation of resting thymocytes, which might explain the enhanced FIV replication observed. Together, these data suggest that feDCs have abilities similar to those shown for simian and human DCs in the interaction with leukocytes. This system is suitable for further investigations of the interplay of DC and T cells during FIV infection in vitro.

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