Phenotypic modulation and cytokine profiles of antigen presenting cells by European subtype 1 and 3 porcine reproductive and respiratory syndrome virus strains in vitro and in vivo

2013 ◽  
Vol 167 (3-4) ◽  
pp. 638-650 ◽  
Author(s):  
Eefke Weesendorp ◽  
Norbert Stockhofe-Zurwieden ◽  
Ditta J. Popma-De Graaf ◽  
Helmi Fijten ◽  
Johanna M.J. Rebel
Keyword(s):  
Antigen Presenting Cells ◽  
Respiratory Syndrome Virus ◽  
Phenotypic Modulation ◽  
Cytokine Profiles ◽  
Antigen Presenting ◽  
Virus Strains ◽  
European Subtype

scholarly journals Development of Stable Chimeric IL-15 for Trans-Presentation by the Antigen Presenting Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Manoj Patidar ◽  
Naveen Yadav ◽  
Sarat K. Dalai
Keyword(s):  
T Cells ◽  
T Cell ◽  
Half Life ◽  
Therapeutic Potential ◽  
Chimeric Protein ◽  
Antigen Presenting Cells ◽  
T Cell Response ◽  
Antigen Presenting

IL-15 is one of the important biologics considered for vaccine adjuvant and treatment of cancer. However, a short half-life and poor bioavailability limit its therapeutic potential. Herein, we have structured IL-15 into a chimeric protein to improve its half-life enabling greater bioavailability for longer periods. We have covalently linked IL-15 with IgG2 base to make the IL-15 a stable chimeric protein, which also increased its serum half-life by 40 fold. The dimeric structure of this kind of IgG based biologics has greater stability, resistance to proteolytic cleavage, and less frequent dosing schedule with minimum dosage for achieving the desired response compared to that of their monomeric forms. The structured chimeric IL-15 naturally forms a dimer, and retains its affinity for binding to its receptor, IL-15Rβ. Moreover, with the focused action of the structured chimeric IL-15, antigen-presenting cells (APC) would transpresent chimeric IL-15 along with antigen to the T cell, that will help the generation of quantitatively and qualitatively better antigen-specific memory T cells. In vitro and in vivo studies demonstrate the biological activity of chimeric IL-15 with respect to its ability to induce IL-15 signaling and modulating CD8+ T cell response in favor of memory generation. Thus, a longer half-life, dimeric nature, and anticipated focused transpresentation by APCs to the T cells will make chimeric IL-15 a super-agonist for memory CD8+ T cell responses.

Indirect inhibition of in vivo and in vitro T-cell responses by intravenous immunoglobulins due to impaired antigen presentation

Blood ◽  
2010 ◽  
Vol 115 (9) ◽  
pp. 1727-1734 ◽  
Author(s):  
Éric Aubin ◽  
Réal Lemieux ◽  
Renée Bazin
Keyword(s):  
T Cell ◽  
Antigen Presentation ◽  
T Cell Activation ◽  
T Cell Responses ◽  
Antigen Presenting Cells ◽  
In Vivo Model ◽  
Cell Responses ◽  
Antigen Presenting

Abstract Several clinical studies done with intravenous immunoglobulin (IVIg)–treated autoimmune patients as well as several in vitro studies have revealed that IVIg can reduce polyclonal T-cell activation and modify their cytokine secretion pattern. However, their effect on (auto)antigen-specific T-cell responses has never been addressed directly. In the present work, we used an in vivo model of induction of antigen-specific T-cell responses and an in vitro antigen presentation system to study the effects of IVIg on T-cell responses. The results obtained showed that IVIg inhibited both the in vivo and in vitro antigen-specific T-cell responses but that this effect was the indirect consequence of a reduction in the antigen presentation ability of antigen-presenting cells. The inhibitory effect of IVIg was FcγRIIb-independent, suggesting that IVIg must interfere with activating FcγRs expressed on antigen-presenting cells to reduce their ability to present antigens. Such inhibition of T-cell responses by reducing antigen presentation may therefore contribute to the well-known anti-inflammatory effects of IVIg in autoimmune diseases.

scholarly journals Nanoparticles Engineered as Artificial Antigen-Presenting Cells Induce Human CD4+ and CD8+ Tregs That Are Functional in Humanized Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Sophia Giang ◽  
David A. Horwitz ◽  
Sean Bickerton ◽  
Antonio La Cava
Keyword(s):  
T Cells ◽  
Lupus Erythematosus ◽  
T Regulatory Cells ◽  
Antigen Presenting Cells ◽  
Plga Nanoparticles ◽  
Nsg Mice ◽  
Artificial Antigen ◽  
Antigen Presenting

Artificial antigen-presenting cells (aAPCs) are synthetic versions of naturally occurring antigen-presenting cells (APCs) that, similar to natural APCs, promote efficient T effector cell responses in vitro. This report describes a method to produce acellular tolerogenic aAPCs made of biodegradable poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) and encapsulating IL-2 and TGF-β for a paracrine release to T cells. We document that these aAPCs can induce both human CD4+ and CD8+ T cells to become FoxP3+ T regulatory cells (Tregs). The aAPC NP-expanded human Tregs are functional in vitro and can modulate systemic autoimmunity in vivo in humanized NSG mice. These findings establish a proof-of-concept to use PLGA NPs as aAPCs for the induction of human Tregs in vitro and in vivo, highlighting the immunotherapeutic potential of this targeted approach to repair IL-2 and/or TGF-β defects documented in certain autoimmune diseases such as systemic lupus erythematosus.

scholarly journals A Targeted Vaccine against COVID-19: S1-Fc Vaccine Targeting the Antigen-Presenting Cell Compartment Elicits Protection against SARS-CoV-2 Infection

2020 ◽  
Author(s):  
Andreas Herrmann ◽  
Junki Maruyama ◽  
Chanyu Yue ◽  
Christoph Lahtz ◽  
Heyue Zhou ◽  
...  
Keyword(s):  
Antigen Presenting Cells ◽  
T Cell Response ◽  
Antigen Delivery ◽  
Cell Compartment ◽  
Antigen Presenting Cell ◽  
Live Virus ◽  
Virus Challenge ◽  
Antigen Presenting

AbstractVaccination efficacy is enhanced by targeting the antigen-presenting cell compartment. Here, we show that S1-Fc antigen delivery targeting the FcγR+ antigen-presenting cell compartment elicits anti-SARS-CoV-2 S1-antigen specific IgG production in vivo exerting biologically functional and protective activity against live virus infection, assessed in a stringent experimental virus challenge assay in vitro. The S1-domain of the SARS-CoV-2 spike protein was genetically fused to a human immunoglobulin Fc moiety, which contributes to mediate S1-Fc cellular internalization by FcγR+ antigen-presenting cells. Immediately upon administration intramuscularly, our novel vaccine candidate recombinant rS1-Fc homes to lymph nodes in vivo where FcγR+ antigen-presenting cells reside. Seroconversion is achieved as early as day 7, mounting considerably increased levels of anti-S1 IgGs in vivo. Interestingly, immunization at elevated doses with non-expiring S1-Fc encoding dsDNA favors the education of a desired antigen-specific adaptive T cell response. However, low-dose immunization, safeguarding patient safety, using recombinant rS1-Fc, elicits a considerably elevated protection amplitude against live SARS-CoV-2 infection. Our promising findings on rS1-Fc protein immunization prompted us to further develop an affordable and safe product for delivery to our communities in need for COVID-19 vaccinations.

Boosting In Vivo CAR-Redirected Virus-Specific CTLs With Universal-Artificial Antigen Presenting Cells

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4204-4204
Author(s):  
Ignazio Caruana ◽  
Gerrit Weber ◽  
Barbara Savoldo ◽  
Gianpietro Dotti
Keyword(s):  
Antitumor Activity ◽  
Research Funding ◽  
Antigen Presenting Cells ◽  
Specific Ctls ◽  
Viral Antigens ◽  
Nsg Mice ◽  
Healthy Donors ◽  
Antigen Presenting

Abstract Virus-specific cytotoxic T lymphocytes (CTLs) targeting EBV and/or CMV and engrafted with chimeric antigen receptors (CARs) can receive appropriate costimulation from professional antigen presenting cells (APCs) that process latent viral antigens and can then target tumor cells through their CAR. In a clinical trial in neuroblastoma patients, CAR-redirected virus specific CTLs persisted for over 6 weeks after infusion and produced complete tumor responses in 3/11 patients. To improve the in vivo expansion and persistence of CAR-redirected virus specific CTLs, we determined whether K562 cells engineered to express viral antigens and either CD40L or OX40L can act as universal artificial APCs (aAPCs) to boost CAR-modified virus-specific CTLs in vivo through a cross-presentation mechanism. Using CMV as the viral antigen model, we found that aAPCs/pp65 produce superior in vitro activation of CMV-specific CTLs from seropositive healthy donors (292±56 IFNγ spot forming cells (SFC)/105 cells) than control non modified K562 (83±25 IFNγ SFC/105 cells). The frequency of CMV-CTLs was further enhanced if the aAPC coexpressed CD40L (aAPCs/pp65/CD40L) (502±104 SFC/105 cells; p<0.001) but not by incorporation of OX40L (aAPCs/pp65/OX40L) (357±40 SFC/105 cells) or the combination CD40L/OX40L (477±91 SFC/105 cells). We then assessed whether these aAPCs can boost in vivo CMV-specific CTL responses in NSG mice engrafted with human cells from CMV-seropositive healthy donors. Spleens isolated from mice that had been vaccinated with either aAPCs/pp65 or aAPCs/pp65/CD40L or aAPCs/pp65/OX40L showed an increased frequency of CMV-specific precursors (57±24 vs. 41±14 vs. 35±17 IFNγ-SFC/105 cells) as compared to mice infused with control aAPCs (27±6) (p=0.005). In contrast to the in vitro experiments, the combination in vivo of aAPCs/CD40L/pp65 and aAPCs/OX40L/pp65 elicited the highest number of CMV-specific precursors (101±21 SFC/105 cells). We then tested if CMV-CTLs retained this response to the aAPC vaccine when the CTLs were grafted with a CAR. As a model we used a CAR targeting the neuroblastoma associated antigen GD2. We found that in vitro stimulation with aAPCs/CD40L/OX40L/pp65 promoted the greatest increase of CMV-specific (925±201 IFNγ SFC/105 cells) and CAR-GD2 responses (2725±585 IFNγ SFC/105 cells). The effector function of CAR+ CMV-CTLs was maintained through both their native TCR and their CAR as indicated by cytotoxicity against both GD2+ target cells (CHLA-255=63±14% at a 20:1 E:T ratio) and pp65-infected cells (59±3%); there was no killing of GD2- targets (Raji = 18%±8%) or of CMV uninfected cells (3%±1%). Sustained persistence of CAR+ CMV-CTLs in response to the aAPCs was also maintained in vivo. Thus, vaccination of NSG mice with aAPCs/CD40L/OX40L/pp65 enhanced the frequency of CAR+ CTLs (range 2.4% - 6.25%) as compared to mice vaccinated with control aAPCs (0.98% - 1.08%). IFNγ ELISpot assays confirmed increased functional frequency of both CAR and pp65 mediated recognition of T cells isolated from mice vaccinated with aAPCs/CD40L/OX40L/pp65 against GD2+ targets (71±24 SFC/105 cells) and pp65-infected targets (85±16) as compared to control mice (23±8 and 41±11, respectively) (p=0.048 and p=0.035). Importantly, vaccination increased the antitumor activity of CAR-CTLs in a xenograft model of neuroblastoma since 48% of the mice vaccinated with aAPCs/CD40L/OX40L/pp65 were tumor free by day 40, while mice vaccinated with control aAPCs uniformly succumbed to the tumor (p≤0.037). In conclusion, we have identified a broadly applicable strategy to stimulate CAR redirected virus-specific CTLs in vivo through their native TCR that lengthens their persistence and thereby increases their antitumor activity. Disclosures: Savoldo: Celgene: Patents & Royalties, Research Funding. Dotti:Celgene: Patents & Royalties, Research Funding.

scholarly journals Interaction of Cowpea Mosaic Virus (CPMV) Nanoparticles with Antigen Presenting Cells In Vitro and In Vivo

PLoS ONE ◽  
2009 ◽  
Vol 4 (11) ◽  
pp. e7981 ◽  
Author(s):  
Maria J. Gonzalez ◽  
Emily M. Plummer ◽  
Chris S. Rae ◽  
Marianne Manchester
Keyword(s):  
Mosaic Virus ◽  
Antigen Presenting Cells ◽  
Cowpea Mosaic Virus ◽  
Antigen Presenting

scholarly journals Delivery of the Immunosuppressive Antigen Salp15 to Antigen-Presenting Cells by Salmonella enterica Serovar Typhimurium aroA Mutants

2004 ◽  
Vol 72 (6) ◽  
pp. 3638-3642 ◽  
Author(s):  
Amir-Reza T. Motameni ◽  
Ignacio J. Juncadella ◽  
Shobana K. Ananthanarayanan ◽  
Michael N. Hedrick ◽  
Yvette Huet-Hudson ◽  
...  
Keyword(s):  
T Cell Activation ◽  
Salmonella Enterica ◽  
Cell Activation ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Active Form ◽  
Antigen Presenting Cells ◽  
Serovar Typhimurium ◽  
Antigen Presenting

ABSTRACT A Salmonella enterica serovar Typhimurium aroA-deficient delivery system was used to target the immunosuppressive protein Salp15 to antigen-presenting cells. In vitro and in vivo infections with Salp15-containing Salmonella resulted in an impaired CD4+-T-cell activation, suggesting that the protein was produced by antigen-presenting cells in a physiologically active form.

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