scholarly journals Lipopolysaccharide-Induced In Vivo Activation of Follicular Dendritic Cells is Tumor Necrosis Factor Receptor-1 Independent

2011 ◽  
Vol 295 (1) ◽  
pp. 87-90 ◽  
Author(s):  
Novica M. Milićević ◽  
Živana Milićević ◽  
Jűrgen Westermann
Keyword(s):  
Dendritic Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Follicular Dendritic Cells ◽  
Follicular Dendritic ◽  
Necrosis Factor

scholarly journals Differentiation of follicular dendritic cells and full antibody responses require tumor necrosis factor receptor-1 signaling.

1996 ◽  
Vol 183 (5) ◽  
pp. 2367-2372 ◽  
Author(s):  
M Le Hir ◽  
H Bluethmann ◽  
M H Kosco-Vilbois ◽  
M Müller ◽  
F di Padova ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Tumor Necrosis Factor ◽  
Antibody Response ◽  
Tumor Necrosis ◽  
Germinal Centers ◽  
Follicular Dendritic Cells ◽  
Igg Antibody ◽  
Beta Receptor ◽  
Follicular Dendritic ◽  
Necrosis Factor

Using mice double deficient for tumor necrosis factor (TNF) and lymphotoxin alpha (LT alpha), we demonstrated that TNF and/or LT alpha are necessary for development of a normal splenic microarchitecture and for isotype switch after immunization with sheep red blood cells (SRBC). In the present study, we extended these observations by determining which TNF receptor (TNFR) is involved in morphological and functional differentiation of the spleen. Spleen morphology and antibody response were investigated in wild-type, TNFR1-/-, TNFR2-/- and TNF/LT alpha-/- mice immunized with SRBC. TNF/LT alpha-/- mice, which have a complete disruption of the TNF/LT alpha signaling system including the LT beta-receptor pathway, displayed an abnormal microarchitecture, and isotype switch did not take place. TNFR1-/- and TNFR2-/- mice displayed a normal spleen microarchitecture and mounted an IgM and IgG antibody response to SRBC. However, the IgG production in TNFR1-/- mice was minimal, with citers leveling off 6 d after immunization. In this strain, immunofluorescence revealed a lack of follicular dendritic cells (FDC) network, detected with FDC-M1 as well as anti-CR1, and a lack of germinal centers, detected with peanut agglutinin. In conclusion, whereas normal splenic microarchitecture and isotype switch might require the LT beta receptor, differentiation of FDC network, development of germinal centers, and full IgG response depend on signaling via TNFR1.

scholarly journals Posttranscriptional Downregulation of c-IAP2 by the Ubiquitin Protein Ligase c-IAP1 In Vivo

2005 ◽  
Vol 25 (8) ◽  
pp. 3348-3356 ◽  
Author(s):  
Dietrich B. Conze ◽  
Lori Albert ◽  
David A. Ferrick ◽  
David V. Goeddel ◽  
Wen-Chen Yeh ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Homologous Gene ◽  
Necrosis Factor Alpha ◽  
Ubiquitin Protein Ligase ◽  
Signaling Complex ◽  
Subsequent Degradation ◽  
Necrosis Factor

ABSTRACT Inhibitor of apoptosis proteins (IAPs) c-IAP1 and c-IAP2 were identified as part of the tumor necrosis factor receptor 2 (TNFR2) signaling complex and have been implicated as intermediaries in tumor necrosis factor alpha signaling. Like all RING domain-containing IAPs, c-IAP1 and c-IAP2 have ubiquitin protein ligase (E3) activity. To explore the function of c-IAP1 in a physiologic setting, c-IAP1-deficient mice were generated by homologous gene recombination. These animals are viable and have no obvious sensitization to proapoptotic stimuli. Cells from c-IAP1−/− mice do, however, express markedly elevated levels of c-IAP2 protein in the absence of increased c-IAP2 mRNA. In contrast to reports implicating c-IAPs in the activation of NF-κB, resting and cytokine-induced NF-κB activation was not impaired in c-IAP1-deficient cells. Transient transfection studies with wild-type and E3-defective c-IAP1 revealed that c-IAP2 is a direct target for c-IAP1-mediated ubiquitination and subsequent degradation, which are potentiated by the adaptor function of TRAF2. Thus, the c-IAPs represent a pair of TNFR-associated ubiquitin protein ligases in which one regulates the expression of the other by a posttranscriptional and E3-dependent mechanism.

scholarly journals Tumor Necrosis Factor Receptor 1 Expression Is Upregulated in Dendritic Cells in Patients with Chronic HCV Who Respond to Therapy

2010 ◽  
Vol 2010 ◽  
pp. 1-10
Author(s):  
Raul Cubillas ◽  
Katherine Kintner ◽  
Frances Phillips ◽  
Nitin J. Karandikar ◽  
Dwain L. Thiele ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Mononuclear Cells ◽  
Tumor Necrosis Factor Receptor ◽  
Mrna Levels ◽  
Specific Subset ◽  
Significant Difference ◽  
Chronic Hcv ◽  
Necrosis Factor

The present studies assessed the level of tumor necrosis factor receptor (TNFR) expression in peripheral blood mononuclear cells (PBMCs) subsets from patients with chronic HCV undergoing interferon /ribavirin-based therapy (Ifn/R). Methods. TNFR family member mRNA expression was determined using quantitative real-time PCR assays (RTPCRs) in PBMC from 39 HCV+ patients and 21 control HCV patients. Further subset analysis of HCV + patients (untreated (U), sustained virological responders (SVR), and nonresponders (NR)/relapsers (Rel)) PBMC was performed via staining with anti-CD123, anti-CD33, anti-TNFR1 or via RTPCR for TNFR1 mRNA. Results. A similar level of TNFR1 mRNA in PBMC from untreated HCV+ genotype 1 patients and controls was noted. TNFR1 and TNFR2 mRNA levels in PBMC from HCV+ patients with SVR were statistically different than levels in HCV() patients. A significant difference was noted between the peak values of TNFR1 of the CD123+ PBMC isolated from SVR and the NR/Rel. Conclusion. Upregulation of TNFR1 expression, occurring in a specific subset of CD123+ dendritic cells, appeared in HCV+ patients with SVR.

IN VIVO SOLUBLE TUMOR NECROSIS FACTOR RECEPTOR RELEASE IN OKT3-TREATED PATIENTS

1995 ◽  
Vol 59 (10) ◽  
pp. 1470-1475 ◽  
Author(s):  
André Herbelin ◽  
Lucienne Chatenoud ◽  
Pascale Roux-Lombard ◽  
Donat De Groote ◽  
Christophe Legendre ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Necrosis Factor

scholarly journals Repetitive Injections of Dendritic Cells Matured with Tumor Necrosis Factor α Induce Antigen-specific Protection of Mice from Autoimmunity

2001 ◽  
Vol 195 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Mauritius Menges ◽  
Susanne Rößner ◽  
Constanze Voigtländer ◽  
Heike Schindler ◽  
Nicole A. Kukutsch ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Cell Immunity ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Mature dendritic cells (DCs) are believed to induce T cell immunity, whereas immature DCs induce T cell tolerance. Here we describe that injections of DCs matured with tumor necrosis factor (TNF)-α (TNF/DCs) induce antigen-specific protection from experimental autoimmune encephalomyelitis (EAE) in mice. Maturation by TNF-α induced high levels of major histocompatibility complex class II and costimulatory molecules on DCs, but they remained weak producers of proinflammatory cytokines. One injection of such TNF/DCs pulsed with auto-antigenic peptide ameliorated the disease score of EAE. This could not be observed with immature DCs or DCs matured with lipopolysaccharide (LPS) plus anti-CD40. Three consecutive injections of peptide-pulsed TNF/DCs derived from wild-type led to the induction of peptide-specific predominantly interleukin (IL)-10–producing CD4+ T cells and complete protection from EAE. Blocking of IL-10 in vivo could only partially restore the susceptibility to EAE, suggesting an important but not exclusive role of IL-10 for EAE prevention. Notably, the protection was peptide specific, as TNF/DCs pulsed with unrelated peptide could not prevent EAE. In conclusion, this study describes that stimulation by TNF-α results in incompletely matured DCs (semi-mature DCs) which induce peptide-specific IL-10–producing T cells in vivo and prevent EAE.

scholarly journals A Critical Role of the p75 Tumor Necrosis Factor Receptor (p75TNF-R) in Organ Inflammation Independent of  TNF, Lymphotoxin α, or the p55TNF-R

1998 ◽  
Vol 188 (7) ◽  
pp. 1343-1352 ◽  
Author(s):  
Eleni Douni ◽  
George Kollias
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Critical Role ◽  
Tumor Necrosis Factor Receptor ◽  
Peripheral Blood Mononuclear ◽  
Enhanced Production ◽  
Wide Range ◽  
Lymphotoxin Α ◽  
Necrosis Factor

Despite overwhelming evidence that enhanced production of the p75 tumor necrosis factor receptor (p75TNF-R) accompanies development of specific human inflammatory pathologies such as multi-organ failure during sepsis, inflammatory liver disease, pancreatitis, respiratory distress syndrome, or AIDS, the function of this receptor remains poorly defined in vivo. We show here that at levels relevant to human disease, production of the human p75TNF-R in transgenic mice results in a severe inflammatory syndrome involving mainly the pancreas, liver, kidney, and lung, and characterized by constitutively increased NF-κB activity in the peripheral blood mononuclear cell compartment. This process is shown to evolve independently of the presence of TNF, lymphotoxin α, or the p55TNF-R, although coexpression of a human TNF transgene accelerated pathology. These results establish an independent role for enhanced p75TNF-R production in the pathogenesis of inflammatory disease and implicate the direct involvement of this receptor in a wide range of human inflammatory pathologies.

scholarly journals Role of SODD in Regulation of Tumor Necrosis Factor Responses

2003 ◽  
Vol 23 (11) ◽  
pp. 4026-4033 ◽  
Author(s):  
Hidetoshi Takada ◽  
Nien-Jung Chen ◽  
Christine Mirtsos ◽  
Shinobu Suzuki ◽  
Nobutaka Suzuki ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Signaling Proteins ◽  
Ligand Stimulation ◽  
Cytotoxic Responses ◽  
Necrosis Factor

ABSTRACT Signaling from tumor necrosis factor receptor type 1 (TNFR1) can elicit potent inflammatory and cytotoxic responses that need to be properly regulated. It was suggested that the silencer of death domains (SODD) protein constitutively associates intracellularly with TNFR1 and inhibits the recruitment of cytoplasmic signaling proteins to TNFR1 to prevent spontaneous aggregation of the cytoplasmic death domains of TNFR1 molecules that are juxtaposed in the absence of ligand stimulation. In this study, we demonstrate that mice lacking SODD produce larger amounts of cytokines in response to in vivo TNF challenge. SODD-deficient macrophages and embryonic fibroblasts also show altered responses to TNF. TNF-induced activation of NF-κB is accelerated in SODD-deficient cells, but TNF-induced c-Jun N-terminal kinase activity is slightly repressed. Interestingly, the apoptotic arm of TNF signaling is not hyperresponsive in the SODD-deficient cells. Together, these results suggest that SODD is critical for the regulation of TNF signaling.

scholarly journals Activated T Cells Induce Macrophages To Produce NO and Control Leishmania major in the Absence of Tumor Necrosis Factor Receptor p55

2000 ◽  
Vol 68 (3) ◽  
pp. 1428-1434 ◽  
Author(s):  
Michelle Nashleanas ◽  
Phillip Scott
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Leishmania Major ◽  
Tumor Necrosis Factor Receptor ◽  
No Production ◽  
Activated T Cells ◽  
Necrosis Factor

ABSTRACT The ability to activate macrophages in vitro for nitric oxide production and killing of Leishmania major parasites is dependent on tumor necrosis factor, although L. major-infected mice lacking the TNF receptor p55 (TNFRp55−/− mice) or both the TNFRp55 and TNFRp75 (TNFRp55p75−/− mice) are able to produce NO in vivo and eliminate the parasites. Here we report that activated T cells cocultured with macrophages results in TNFR-independent activation sufficient to control parasites and that both CD40/CD40L and LFA-1 contribute to T-cell-mediated macrophage activation. Thus, anti-CD3-stimulated T cells activated TNFR-deficient macrophages, while T cells from CD40L−/− mice were partially defective in triggering NO production by TNFRp55p75−/− macrophages. Moreover, in the presence of gamma interferon, anti-CD40 monoclonal antibody (MAb) activated TNFR-deficient macrophages. Finally, MAb blockade of LFA-1 completely inhibited macrophage NO production. Our data indicate that T cells can activate macrophages in the absence of TNF, thus providing a mechanism for how TNFR-deficient mice can control intracellular pathogens.

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