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Article ; Online: A Restricted Role for FcγR in the Regulation of Adaptive Immunity.

Fransen, Marieke F / Benonisson, Hreinn / van Maren, Wendy W / Sow, Heng Sheng / Breukel, Cor / Linssen, Margot M / Claassens, Jill W C / Brouwers, Conny / van der Kaa, Jos / Camps, Marcel / Kleinovink, Jan Willem / Vonk, Kelly K / van Heiningen, Sandra / Klar, Ngaisah / van Beek, Lianne / van Harmelen, Vanessa / Daxinger, Lucia / Nandakumar, Kutty S / Holmdahl, Rikard /

Coward, Chris / Lin, Qingshun / Hirose, Sachiko / Salvatori, Daniela / van Hall, Thorbald / van Kooten, Cees / Mastroeni, Piero / Ossendorp, Ferry / Verbeek, J Sjef

Journal of immunology (Baltimore, Md. : 1950)

2018 Volume 200, Issue 8, Page(s) 2615–2626

Abstract: By their interaction with IgG immune complexes, FcγR and complement link innate and adaptive immunity, showing functional redundancy. In complement-deficient mice, IgG downstream effector functions are often impaired, as well as adaptive immunity. Based ... ...

Abstract	By their interaction with IgG immune complexes, FcγR and complement link innate and adaptive immunity, showing functional redundancy. In complement-deficient mice, IgG downstream effector functions are often impaired, as well as adaptive immunity. Based on a variety of model systems using FcγR-knockout mice, it has been concluded that FcγRs are also key regulators of innate and adaptive immunity; however, several of the model systems underpinning these conclusions suffer from flawed experimental design. To address this issue, we generated a novel mouse model deficient for all FcγRs (FcγRI/II/III/IV
Language	English
Publishing date	2018-03-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1700429
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Article ; Online: Linking T cell epitopes to a common linear B cell epitope: A targeting and adjuvant strategy to improve T cell responses.

Mangsbo, Sara M / Fletcher, Erika A K / van Maren, Wendy W C / Redeker, Anke / Cordfunke, Robert A / Dillmann, Inken / Dinkelaar, Jasper / Ouchaou, Kahina / Codee, Jeroen D C / van der Marel, Gijs A / Hoogerhout, Peter / Melief, Cornelis J M / Ossendorp, Ferry / Drijfhout, Jan W

Molecular immunology

2017 Volume 93, Page(s) 115–124

Abstract: Immune complexes are potent mediators of cellular immunity and have been extensively studied for their disease mediating properties in humans and for their role in anti-cancer immunity. However, a viable approach to use antibody-complexed antigen as ... ...

Abstract	Immune complexes are potent mediators of cellular immunity and have been extensively studied for their disease mediating properties in humans and for their role in anti-cancer immunity. However, a viable approach to use antibody-complexed antigen as vehicle for specific immunotherapy has not yet reached clinical use. Since virtually all people have endogenous antibodies against tetanus toxoid (TTd), such commonly occurring antibodies are promising candidates to utilize for immune modulation. As an initial proof-of-concept we investigated if anti-tetanus IgG could induce potent cross-presentation of a conjugate with SIINFEKL, a MHC class I presented epitope of ovalbumin (OVA), to TTd. This protein conjugate enhanced OVA-specific CD8+ T cell responses when administrated to seropositive mice. Since TTd is poorly defined, we next investigated whether a synthetic peptide-peptide conjugate, with a chemically defined linear B cell epitope of tetanus toxin (TTx) origin, could improve cellular immune responses. Herein we identify one linear B cell epitope, here after named MTTE thru a screening of overlapping peptides from the alpha and beta region of TTx, and by assessment of the binding of pooled IgG, or individual human IgG from high-titer TTd vaccinated donors, to these peptides. Subsequently, we developed a chemical protocol to synthesize defined conjugates containing multiple copies of MTTE covalently attached to one or more T cell epitopes of choice. To demonstrate the potential of the above approach we showed that immune complexes of anti-MTTE antibodies with MTTE-containing conjugates are able to induce DC and T cell activation using model antigens.
MeSH term(s)	Amino Acid Sequence ; Animals ; Antigen-Antibody Complex/immunology ; Cross-Priming/immunology ; Dendritic Cells/immunology ; Epitopes, B-Lymphocyte ; Epitopes, T-Lymphocyte/immunology ; H-2 Antigens/immunology ; Humans ; Hybridomas ; Immunoconjugates/immunology ; Immunoglobulin G/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Ovalbumin/immunology ; Peptide Fragments/immunology ; Tetanus Toxoid/chemistry ; Tetanus Toxoid/immunology ; Vaccination
Chemical Substances	Antigen-Antibody Complex ; Epitopes, B-Lymphocyte ; Epitopes, T-Lymphocyte ; H-2 Antigens ; H-2Kb protein, mouse ; Immunoconjugates ; Immunoglobulin G ; OVA-8 ; Peptide Fragments ; Tetanus Toxoid ; Ovalbumin (9006-59-1)
Language	English
Publishing date	2017-11-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	424427-8
ISSN	1872-9142 ; 0161-5890
ISSN (online)	1872-9142
ISSN	0161-5890
DOI	10.1016/j.molimm.2017.11.004
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Article ; Online: Machine Learning Used to Compare the Diagnostic Accuracy of Risk Factors, Clinical Signs and Biomarkers and to Develop a New Prediction Model for Neonatal Early-onset Sepsis.

Stocker, Martin / Daunhawer, Imant / van Herk, Wendy / El Helou, Salhab / Dutta, Sourabh / Schuerman, Frank A B A / van den Tooren-de Groot, Rita K / Wieringa, Jantien W / Janota, Jan / van der Meer-Kappelle, Laura H / Moonen, Rob / Sie, Sintha D / de Vries, Esther / Donker, Albertine E / Zimmerman, Urs / Schlapbach, Luregn J / de Mol, Amerik C / Hoffmann-Haringsma, Angelique / Roy, Madan /

Tomaske, Maren / Kornelisse, René F / van Gijsel, Juliette / Plötz, Frans B / Wellmann, Sven / Achten, Niek B / Lehnick, Dirk / van Rossum, Annemarie M C / Vogt, Julia E

The Pediatric infectious disease journal

2021 Volume 41, Issue 3, Page(s) 248–254

Abstract: ... to clinical signs and RFs for prediction of culture-proven EOS. C-reactive protein and white blood cells were ...

Abstract	Background: Current strategies for risk stratification and prediction of neonatal early-onset sepsis (EOS) are inefficient and lack diagnostic performance. The aim of this study was to use machine learning to analyze the diagnostic accuracy of risk factors (RFs), clinical signs and biomarkers and to develop a prediction model for culture-proven EOS. We hypothesized that the contribution to diagnostic accuracy of biomarkers is higher than of RFs or clinical signs. Study design: Secondary analysis of the prospective international multicenter NeoPInS study. Neonates born after completed 34 weeks of gestation with antibiotic therapy due to suspected EOS within the first 72 hours of life participated. Primary outcome was defined as predictive performance for culture-proven EOS with variables known at the start of antibiotic therapy. Machine learning was used in form of a random forest classifier. Results: One thousand six hundred eighty-five neonates treated for suspected infection were analyzed. Biomarkers were superior to clinical signs and RFs for prediction of culture-proven EOS. C-reactive protein and white blood cells were most important for the prediction of the culture result. Our full model achieved an area-under-the-receiver-operating-characteristic-curve of 83.41% (±8.8%) and an area-under-the-precision-recall-curve of 28.42% (±11.5%). The predictive performance of the model with RFs alone was comparable with random. Conclusions: Biomarkers have to be considered in algorithms for the management of neonates suspected of EOS. A 2-step approach with a screening tool for all neonates in combination with our model in the preselected population with an increased risk for EOS may have the potential to reduce the start of unnecessary antibiotics.
MeSH term(s)	Anti-Bacterial Agents/therapeutic use ; Biomarkers/blood ; C-Reactive Protein/analysis ; Female ; Humans ; Infant ; Infant, Newborn ; Machine Learning ; Male ; Neonatal Sepsis/diagnosis ; Neonatal Sepsis/drug therapy ; Prospective Studies ; ROC Curve ; Risk Factors
Chemical Substances	Anti-Bacterial Agents ; Biomarkers ; C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2021-09-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	392481-6
ISSN	1532-0987 ; 0891-3668
ISSN (online)	1532-0987
ISSN	0891-3668
DOI	10.1097/INF.0000000000003344
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Article ; Online: C-Reactive Protein, Procalcitonin, and White Blood Count to Rule Out Neonatal Early-onset Sepsis Within 36 Hours: A Secondary Analysis of the Neonatal Procalcitonin Intervention Study.

Stocker, Martin / van Herk, Wendy / El Helou, Salhab / Dutta, Sourabh / Schuerman, Frank A B A / van den Tooren-de Groot, Rita K / Wieringa, Jantien W / Janota, Jan / van der Meer-Kappelle, Laura H / Moonen, Rob / Sie, Sintha D / de Vries, Esther / Donker, Albertine E / Zimmerman, Urs / Schlapbach, Luregn J / de Mol, Amerik C / Hoffman-Haringsma, Angelique / Roy, Madan / Tomaske, Maren /

F Kornelisse, René / van Gijsel, Juliette / Visser, Eline G / Plötz, Frans B / Heath, Paul / Achten, Niek B / Lehnick, Dirk / van Rossum, Annemarie M C

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2020 Volume 73, Issue 2, Page(s) e383–e390

Abstract: ... the diagnostic accuracy of serial measurements of C-reactive protein (CRP), procalcitonin (PCT), and white blood ...

Abstract	Background: Neonatal early-onset sepsis (EOS) is one of the main causes of global neonatal mortality and morbidity, and initiation of early antibiotic treatment is key. However, antibiotics may be harmful. Methods: We performed a secondary analysis of results from the Neonatal Procalcitonin Intervention Study, a prospective, multicenter, randomized, controlled intervention study. The primary outcome was the diagnostic accuracy of serial measurements of C-reactive protein (CRP), procalcitonin (PCT), and white blood count (WBC) within different time windows to rule out culture-positive EOS (proven sepsis). Results: We analyzed 1678 neonates with 10 899 biomarker measurements (4654 CRP, 2047 PCT, and 4198 WBC) obtained within the first 48 hours after the start of antibiotic therapy due to suspected EOS. The areas under the curve (AUC) comparing no sepsis vs proven sepsis for maximum values of CRP, PCT, and WBC within 36 hours were 0.986, 0.921, and 0.360, respectively. The AUCs for CRP and PCT increased with extended time frames up to 36 hours, but there was no further difference between start to 36 hours vs start to 48 hours. Cutoff values at 16 mg/L for CRP and 2.8 ng/L for PCT provided a sensitivity of 100% for discriminating no sepsis vs proven sepsis. Conclusions: Normal serial CRP and PCT measurements within 36 hours after the start of empiric antibiotic therapy can exclude the presence of neonatal EOS with a high probability. The negative predictive values of CRP and PCT do not increase after 36 hours.
MeSH term(s)	Biomarkers ; C-Reactive Protein/analysis ; Calcitonin ; Humans ; Infant, Newborn ; Neonatal Sepsis/diagnosis ; Procalcitonin ; Prospective Studies ; ROC Curve ; Sepsis/diagnosis
Chemical Substances	Biomarkers ; Procalcitonin ; Calcitonin (9007-12-9) ; C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2020-09-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciaa876
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Zs.A 1505: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: IgG-mediated anaphylaxis to a synthetic long peptide vaccine containing a B cell epitope can be avoided by slow-release formulation.

Quakkelaar, Esther D / Fransen, Marieke F / van Maren, Wendy W C / Vaneman, Joost / Loof, Nikki M / van Heiningen, Sandra H / Verbeek, J Sjef / Ossendorp, Ferry / Melief, Cornelis J M

Journal of immunology (Baltimore, Md. : 1950)

2014 Volume 192, Issue 12, Page(s) 5813–5820

Abstract: Synthetic long peptides (SLP) are a promising vaccine modality to induce therapeutic T cell responses in patients with chronic infections and tumors. We studied different vaccine formulations in mice using SLP derived from carcinoembryonic Ag. We ... ...

Abstract	Synthetic long peptides (SLP) are a promising vaccine modality to induce therapeutic T cell responses in patients with chronic infections and tumors. We studied different vaccine formulations in mice using SLP derived from carcinoembryonic Ag. We discovered that one of the SLP contains a linear Ab epitope in combination with a CD4 epitope. Repeated vaccination with this carcinoembryonic Ag SLP in mice shows improved T cell responses and simultaneously induced high titers of peptide-specific Abs. These Abs resulted in unexpected anaphylaxis after a third or subsequent vaccinations with the SLP when formulated in saline. Administration of low SLP doses in the slow-release vehicle IFA prevented the anaphylaxis after repeated vaccination. This study underscores both the immunogenicity of SLP vaccination, for inducing T cell as well as B cell responses, and the necessity of safe administration routes.
MeSH term(s)	Anaphylaxis/immunology ; Anaphylaxis/prevention & control ; Animals ; Carcinoembryonic Antigen/immunology ; Carcinoembryonic Antigen/pharmacology ; Delayed-Action Preparations/pharmacology ; Epitopes, B-Lymphocyte/immunology ; Epitopes, B-Lymphocyte/pharmacology ; Female ; Immunoglobulin G/immunology ; Mice ; Mice, Knockout ; Peptides/immunology ; Peptides/pharmacology ; Vaccination/methods ; Vaccines/pharmacology
Chemical Substances	Carcinoembryonic Antigen ; Delayed-Action Preparations ; Epitopes, B-Lymphocyte ; Immunoglobulin G ; Peptides ; Vaccines
Language	English
Publishing date	2014-06-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1302337
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Ud II Zs.37: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Multifaceted effects of synthetic TLR2 ligand and Legionella pneumophilia on Treg-mediated suppression of T cell activation.

van Maren, Wendy W C / Nierkens, Stefan / Toonen, Liza W / Bolscher, Judith M / Sutmuller, Roger P M / Adema, Gosse J

BMC immunology

2011 Volume 12, Page(s) 23

Abstract: Background: Regulatory T cells (Treg) play a crucial role in maintaining immune homeostasis and self-tolerance. The immune suppressive effects of Tregs should however be limited in case effective immunity is required against pathogens or cancer cells. ... ...

Abstract	Background: Regulatory T cells (Treg) play a crucial role in maintaining immune homeostasis and self-tolerance. The immune suppressive effects of Tregs should however be limited in case effective immunity is required against pathogens or cancer cells. We previously found that the Toll-like receptor 2 (TLR2) agonist, Pam3CysSK4, directly stimulated Tregs to expand and temporarily abrogate their suppressive capabilities. In this study, we evaluate the effect of Pam3CysSK4 and Legionella pneumophila, a natural TLR2 containing infectious agent, on effector T (Teff) cells and dendritic cells (DCs) individually and in co-cultures with Tregs. Results: TLR2 agonists can directly provide a co-stimulatory signal inducing enhanced proliferation and cytokine production of naive CD4+ Teff cells. With respect to cytokine production, DCs appear to be most sensitive to low amounts of TLR agonists. Using wild type and TLR2-deficient cells in Treg suppression assays, we accordingly show that all cells (e.g. Treg, Teff cells and DCs) contributed to overcome Treg-mediated suppression of Teff cell proliferation. Furthermore, while TLR2-stimulated Tregs readily lost their ability to suppress Teff cell proliferation, cytokine production by Teff cells was still suppressed. Similar results were obtained upon stimulation with TLR2 ligand containing bacteria, Legionella pneumophila. Conclusions: These findings indicate that both synthetic and natural TLR2 agonists affect DCs, Teff cells and Treg directly, resulting in multi-modal modulation of Treg-mediated suppression of Teff cells. Moreover, Treg-mediated suppression of Teff cell proliferation is functionally distinct from suppression of cytokine secretion.
MeSH term(s)	Animals ; Cells, Cultured ; Coculture Techniques ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Dendritic Cells/pathology ; Immunosuppression Therapy ; Legionella pneumophila/immunology ; Legionella pneumophila/pathogenicity ; Legionnaires' Disease/drug therapy ; Legionnaires' Disease/immunology ; Lipopeptides/pharmacology ; Lymphocyte Activation/drug effects ; Mice ; Mice, Inbred C57BL ; T-Lymphocyte Subsets/drug effects ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism ; T-Lymphocyte Subsets/pathology ; T-Lymphocytes, Regulatory/drug effects ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; T-Lymphocytes, Regulatory/pathology ; Toll-Like Receptor 2/agonists ; Toll-Like Receptor 2/immunology ; Toll-Like Receptor 2/metabolism
Chemical Substances	Lipopeptides ; Pam(3)CSK(4) peptide ; Tlr2 protein, mouse ; Toll-Like Receptor 2
Language	English
Publishing date	2011-03-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2041500-X
ISSN	1471-2172 ; 1471-2172
ISSN (online)	1471-2172
ISSN	1471-2172
DOI	10.1186/1471-2172-12-23
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Article: Linking T cell epitopes to a common linear B cell epitope: A targeting and adjuvant strategy to improve T cell responses

Mangsbo, Sara M / Erika A.K. Fletcher / Wendy W.C. van Maren / Anke Redeker / Robert A. Cordfunke / Inken Dillmann / Jasper Dinkelaar / Kahina Ouchaou / Jeroen D.C. Codee / Gijs A. van der Marel / Peter Hoogerhout / Cornelis J.M. Melief / Ferry Ossendorp / Jan W. Drijfhout

Molecular Immunology. 2018 Jan., v. 93

2018

Abstract	Immune complexes are potent mediators of cellular immunity and have been extensively studied for their disease mediating properties in humans and for their role in anti-cancer immunity. However, a viable approach to use antibody-complexed antigen as vehicle for specific immunotherapy has not yet reached clinical use. Since virtually all people have endogenous antibodies against tetanus toxoid (TTd), such commonly occurring antibodies are promising candidates to utilize for immune modulation. As an initial proof-of-concept we investigated if anti-tetanus IgG could induce potent cross-presentation of a conjugate with SIINFEKL, a MHC class I presented epitope of ovalbumin (OVA), to TTd. This protein conjugate enhanced OVA-specific CD8+ T cell responses when administrated to seropositive mice. Since TTd is poorly defined, we next investigated whether a synthetic peptideâpeptide conjugate, with a chemically defined linear B cell epitope of tetanus toxin (TTx) origin, could improve cellular immune responses. Herein we identify one linear B cell epitope, here after named MTTE thru a screening of overlapping peptides from the alpha and beta region of TTx, and by assessment of the binding of pooled IgG, or individual human IgG from high-titer TTd vaccinated donors, to these peptides. Subsequently, we developed a chemical protocol to synthesize defined conjugates containing multiple copies of MTTE covalently attached to one or more T cell epitopes of choice. To demonstrate the potential of the above approach we showed that immune complexes of anti-MTTE antibodies with MTTE-containing conjugates are able to induce DC and T cell activation using model antigens.
Keywords	B-lymphocytes ; CD8-positive T-lymphocytes ; adjuvants ; antibodies ; antigen-antibody complex ; cell-mediated immunity ; chemical bonding ; conjugated proteins ; epitopes ; humans ; immunoglobulin G ; immunomodulation ; immunotherapy ; mice ; models ; ovalbumin ; people ; peptides ; screening ; seroprevalence ; tetanus
Language	English
Dates of publication	2018-01
Size	p. 115-124.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	424427-8
ISSN	1872-9142 ; 0161-5890
ISSN (online)	1872-9142
ISSN	0161-5890
DOI	10.1016/j.molimm.2017.11.004
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Zs.A 166: Show issues

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Article ; Online: Circulating specific antibodies enhance systemic cross-priming by delivery of complexed antigen to dendritic cells in vivo.

van Montfoort, Nadine / Mangsbo, Sara M / Camps, Marcel G M / van Maren, Wendy W C / Verhaart, Ingrid E C / Waisman, Ari / Drijfhout, Jan Wouter / Melief, Cornelis J M / Verbeek, J Sjef / Ossendorp, Ferry

European journal of immunology

2012 Volume 42, Issue 3, Page(s) 598–606

Abstract: Increasing evidence suggests that antibodies can have stimulatory effects on T-cell immunity. However, the contribution of circulating antigen-specific antibodies on MHC class I cross-priming in vivo has not been conclusively established. Here, we ... ...

Abstract	Increasing evidence suggests that antibodies can have stimulatory effects on T-cell immunity. However, the contribution of circulating antigen-specific antibodies on MHC class I cross-priming in vivo has not been conclusively established. Here, we defined the role of circulating antibodies in cross-presentation of antigen to CD8(+) T cells. Mice with hapten-specific circulating antibodies, but naϊve for the T-cell antigen, were infused with haptenated antigen and CD8(+) T-cell induction was measured. Mice with circulating hapten-specific antibodies showed significantly enhanced cross-presentation of the injected antigen compared with mice that lacked these antibodies. The enhanced cross-presentation in mice with circulating antigen-specific antibodies was associated with improved antigen capture by APCs. Importantly, CD11c(+) APCs were responsible for the enhanced and sustained cross-presentation, although CD11c(-) APCs had initially captured a significant amount of the injected antigen. Thus, in vivo formation of antigen-antibody immune complexes improves MHC class I cross-presentation, and CD8(+) T-cell activation, demonstrating that humoral immunity can aid the initiation of systemic cellular immunity. These findings have important implications for the understanding of the action of therapeutic antibodies against tumor-associated antigens intensively used in the clinic nowadays.
MeSH term(s)	Animals ; Antigen-Antibody Complex/immunology ; Antigens, Neoplasm/immunology ; CD11c Antigen/immunology ; CD8-Positive T-Lymphocytes/cytology ; CD8-Positive T-Lymphocytes/immunology ; Cross-Priming/immunology ; Dendritic Cells/cytology ; Dendritic Cells/immunology ; Flow Cytometry ; Haptens/immunology ; Histocompatibility Antigens Class I/immunology ; Immunity, Cellular/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Ovalbumin/immunology ; Serum Albumin, Bovine/immunology
Chemical Substances	Antigen-Antibody Complex ; Antigens, Neoplasm ; CD11c Antigen ; Haptens ; Histocompatibility Antigens Class I ; Serum Albumin, Bovine (27432CM55Q) ; Ovalbumin (9006-59-1)
Language	English
Publishing date	2012-03
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120108-6
ISSN	1521-4141 ; 0014-2980
ISSN (online)	1521-4141
ISSN	0014-2980
DOI	10.1002/eji.201141613
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Zs.A 489: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Toll-like receptor signalling on Tregs: to suppress or not to suppress?

van Maren, Wendy W C / Jacobs, Joannes F M / de Vries, I Jolanda M / Nierkens, Stefan / Adema, Gosse J

Immunology

2008 Volume 124, Issue 4, Page(s) 445–452

Abstract: To balance self-tolerance and immunity against pathogens or tumours, the immune system depends on both activation mechanisms and down-regulatory mechanisms. Immunologists have long been focusing on activation mechanisms, and a major breakthrough was the ... ...

Abstract	To balance self-tolerance and immunity against pathogens or tumours, the immune system depends on both activation mechanisms and down-regulatory mechanisms. Immunologists have long been focusing on activation mechanisms, and a major breakthrough was the identification of the Toll-like receptor (TLR) family of proteins. TLRs recognize conserved molecular patterns present on pathogens, including bacteria, viruses, fungi and protozoa. Pathogen recognition via TLRs activates the innate as well as the adaptive immune response. The discovery of a suppressive T-cell subset that constitutively expresses the interleukin (IL)-2 receptor alpha-chain (CD25) has boosted efforts to investigate the negative regulation of immune responses. It is now well appreciated that these regulatory T cells (Tregs) play a pivotal role in controlling immune function. Interestingly, recent studies revealed that TLR2 signalling affects Treg expansion and function. This review will focus on the presence and influence of different TLRs on T lymphocytes, including Tregs, and their role in cancer.
MeSH term(s)	Humans ; Immune Tolerance/immunology ; Neoplasms/immunology ; Signal Transduction/immunology ; T-Lymphocyte Subsets/immunology ; T-Lymphocytes, Regulatory/immunology ; Toll-Like Receptors/immunology
Chemical Substances	Toll-Like Receptors
Language	English
Publishing date	2008-06-28
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	80124-0
ISSN	1365-2567 ; 0019-2805 ; 0953-4954
ISSN (online)	1365-2567
ISSN	0019-2805 ; 0953-4954
DOI	10.1111/j.1365-2567.2008.02871.x
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Article: Toll-like receptor signalling on Tregs: to suppress or not to suppress

van Maren, Wendy W.C / Jacobs, Joannes F.M / de Vries, I. Jolanda M / Nierkens, Stefan / Adema, Gosse J

Immunology. 2008 Aug., v. 124, no. 4

2008

Abstract	To balance self-tolerance and immunity against pathogens or tumours, the immune system depends on both activation mechanisms and down-regulatory mechanisms. Immunologists have long been focusing on activation mechanisms, and a major breakthrough was the identification of the Toll-like receptor (TLR) family of proteins. TLRs recognize conserved molecular patterns present on pathogens, including bacteria, viruses, fungi and protozoa. Pathogen recognition via TLRs activates the innate as well as the adaptive immune response. The discovery of a suppressive T-cell subset that constitutively expresses the interleukin (IL)-2 receptor α-chain (CD25) has boosted efforts to investigate the negative regulation of immune responses. It is now well appreciated that these regulatory T cells (Tregs) play a pivotal role in controlling immune function. Interestingly, recent studies revealed that TLR2 signalling affects Treg expansion and function. This review will focus on the presence and influence of different TLRs on T lymphocytes, including Tregs, and their role in cancer.
Keywords	neoplasms
Language	English
Dates of publication	2008-08
Size	p. 445-452.
Publisher	Blackwell Publishing Ltd
Publishing place	Oxford, UK
Document type	Article
ZDB-ID	80124-0
ISSN	1365-2567 ; 0019-2805 ; 0953-4954
ISSN (online)	1365-2567
ISSN	0019-2805 ; 0953-4954
DOI	10.1111/j.1365-2567.2008.02871.x
Database	NAL-Catalogue (AGRICOLA)

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