Expression of relB transcripts during lymphoid organ development: specific expression in dendritic antigen-presenting cells

Development ◽  
1993 ◽  
Vol 118 (4) ◽  
pp. 1221-1231 ◽  
Author(s):  
D. Carrasco ◽  
R.P. Ryseck ◽  
R. Bravo
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Signal Transduction Pathway ◽  
Antigen Presenting Cells ◽  
Lymphoid Organ ◽  
Lymphoid Tissues ◽  
Mouse Development ◽  
Specific Expression ◽  
Dendritic Cell Differentiation ◽  
Antigen Presenting

We have studied the expression of the relB gene during mouse development using in situ hybridization and immunocytochemical analysis. The results show that the expression of the relB gene is highly restricted to a subpopulation of cells that colonize the lymphoid tissues and that appear very late during the process of hematopoietic diversification. RNA transcripts of relB are very low or undetectable in early and late embryos. Low relB expression is observed in the thymus at late stages of embryogenesis but rapidly increases after birth. In adult lymphoid tissues, relB is detected in the medullary region of the thymus, the periarterial lymphatic sheaths of the spleen, and the deep cortex of the lymph nodes, which correspond to the regions where T cells of mature phenotype and interdigitating dendritic cells are present. Using double immunofluorescent labeling of thymic cell suspensions, we have identified the interdigitating dendritic cells as the target of RelB expression. These cells are part of a system of antigen-presenting cells that function in the induction of several immune responses, such as, tolerance, sensitization of MHC-restricted T cells, rejection of organ transplants and formation of T-dependent antibodies. Our observations indicate that RelB may play a particular role in the signal transduction pathway that regulate dendritic cell differentiation and its cellular responses.

scholarly journals Dendritic cells are potent antigen-presenting cells for microbial superantigens.

1992 ◽  
Vol 175 (1) ◽  
pp. 267-273 ◽  
Author(s):  
N Bhardwaj ◽  
S M Friedman ◽  
B C Cole ◽  
A J Nisanian
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Antigen Presenting Cells ◽  
Small Subset ◽  
Cell Functions ◽  
Cell Responses ◽  
Antigen Presenting

Dendritic cells are a small subset of human blood mononuclear cells that are potent stimulators of several T cell functions. Here we show they are 10-50-fold more potent than monocytes or B cells in inducing T cell responses to a panel of superantigens. Furthermore, dendritic cells can present femtomolar concentrations of superantigen to T cells even at numbers where other antigen-presenting cells (APCs) are inactive. Although dendritic cells express very high levels of the major histocompatibility complex products that are required to present superantigens, it is only necessary to pulse these APCs for 1 hour with picomolar levels of one superantigen, staphylococcal enterotoxin B, to maximally activate T cells. Our results suggest that very small amounts of superantigen will be immunogenic in vivo if presented on dendritic cells.

C-Type Lectin Receptor Mediated Immune Recognition of ADAMTS13 Promotes HLA-DRB1*11 Dependent Presentation of CUB1-2 Derived Peptides by Dendritic Cells

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 196-196
Author(s):  
Nicoletta Sorvillo ◽  
Simon D van Haren ◽  
Wouter Pos ◽  
Eszter Herczenik ◽  
Rob Fijnheer ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Mhc Class Ii ◽  
Cd4 T Cells ◽  
Antigen Presenting Cells ◽  
Class Ii ◽  
Immune Recognition ◽  
Dependent Manner ◽  
Sirna Silencing ◽  
Antigen Presenting

Abstract Abstract 196 ADAMTS13 is a plasma metalloproteinase that regulates platelet adhesion and aggregation by virtue of its ability to process newly released ultra-large von Willebrand factor (VWF) multimers on the surface of endothelial cells. Autoantibodies directed against ADAMTS13 prohibit the processing of VWF multimers initiating a rare and life-threatening disorder called acquired thrombotic thrombocytopenic purpura (TTP). HLA-DRB1*11 has recently been identified as a risk factor for acquired TTP. This finding implies that formation of autoantibodies towards ADAMTS13 depends on appropriate presentation of ADAMTS13 derived peptides to CD4+ T-cells by antigen presenting cells. Here, we investigate endocytosis of recombinant ADAMTS13 by immature monocyte-derived dendritic cells (iDCs) using flow cytometry and confocal microscopy. Upon incubation of fluorescently labeled-rADAMTS13 with DCs, a time- and concentration dependent uptake of ADAMTS13 was observed. Endocytosis of ADAMTS13 was completely blocked upon addition of EGTA and mannan. We subsequently explored involvement of C-type lectins (CLRs) in the uptake of ADAMTS13 using specific blocking antibodies and siRNA silencing. We found that ADAMTS13 endocytosis was significantly decreased in cells treated with a monoclonal antibody directed towards macrophage mannose receptor (MR). Furthermore siRNA silencing of MR reduced the uptake of ADAMTS13 by dendritic cells. In vitro binding studies revealed that ADAMTS13 interacts with the carbohydrate recognition domains of MR. These data show that ADAMTS13 is internalized by iDCs in a MR-dependent manner. Antigen presenting cells continuously process endogenous and exogenous antigens into small peptides that are loaded on MHC class I or MHC class II for presentation to T lymphocytes. We have recently developed a method to analyze HLA-DR-presented peptide repertoires of dendritic cells pulsed with antigen (van Haren et al., 2011). Here, we addressed which ADAMTS13-derived peptides were presented on MHC class II alleles of a panel of both HLA-DRB1*11 positive and negative donors. Compared to previous studies with model antigens only a limited number of ADAMTS13-derived peptides were presented on MHC class II. Inspection of peptide-profiles obtained from DRB1*11 positive individuals revealed that two antigenic “core” peptides derived from the CUB1-2 domains of ADAMTS13 were presented by a DR11-positive donor. In addition to these immuno-dominant peptides several other peptides were also presented although with a markedly reduced efficiency. Our findings show that DRB1*11 expressing antigen presenting cells preferentially present antigenic “core” peptides derived from the CUB1-2 domains of ADAMTS13. We hypothesize that functional presentation of these peptides on HLA-DRB1*11 contributes to the onset of acquired TTP by stimulating low affinity self-reactive CD4+ T cells that have escaped negative selection in the thymus. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Uptake of HLA Alloantigens via CD89 and CD206 Does Not Enhance Antigen Presentation by Indirect Allorecognition

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Eytan Breman ◽  
Jurjen M. Ruben ◽  
Kees L. Franken ◽  
Mirjam H. M. Heemskerk ◽  
Dave L. Roelen ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Antigen Presentation ◽  
Antigen Presenting Cells ◽  
Mannose Receptor ◽  
Class Ii ◽  
Hla Class Ii ◽  
Indirect Allorecognition ◽  
Antigen Presenting

In organ transplantation, alloantigens are taken up by antigen presenting cells and presented via the indirect pathway to T-cells which in turn can induce allograft rejection. Monitoring of these T-cells is of major importance; however no reliable assay is available to routinely monitor indirect allorecognition. Recently we showed that HLA monomers can be successfully used to monitor indirect allorecognition. Targeting antigens to endocytic receptors on antigen presenting cells may further enhance the presentation of antigens via HLA class II and improve the efficiency of this assay. In the current study we explored targeting of HLA monomers to either CD89 expressing monocytes or mannose receptor expressing dendritic cells. Monomer-antibody complexes were generated using biotin-labeled monomers and avidin labeling of the antibodies. We demonstrate that targeting the complexes to these receptors resulted in a dose-dependent HLA class II mediated presentation to a T-cell clone. The immune-complexes were efficiently taken up and presented to T-cells. However, the level of T-cell reactivity was similar to that when only exogenous antigen was added. We conclude that HLA-A2 monomers targeted for presentation through CD89 on monocytes or mannose receptor on dendritic cells lead to proper antigen presentation but do not enhance indirect allorecognition via HLA-DR.

Antigen-presenting Cells in Human Radicular Granulomas

2008 ◽  
Vol 87 (6) ◽  
pp. 553-557 ◽  
Author(s):  
T. Kaneko ◽  
T. Okiji ◽  
R. Kaneko ◽  
J.E. Nör ◽  
H. Suda
Keyword(s):  
Electron Microscopy ◽  
T Cells ◽  
Dendritic Cells ◽  
Antigen Presenting Cells ◽  
Gold Particles ◽  
Immunological Responses ◽  
Hla Dr ◽  
Transmission Electron ◽  
Antigen Presenting ◽  
Cytoplasmic Processes

Substantial numbers of dendritic cells have been detected in radicular granulomas. To test the hypothesis that local antigen presentation from dendritic cells to T-cells is involved critically in immunological responses within radicular granulomas, we compared characteristics of dendritic cells and macrophages by morphological and biological analyses. Under light microscopy, HLA-DR+ and CD68+ cells showed diverse profiles, including dendritic-shaped cells. Transmission electron microscopy revealed that HLA-DR+ dendritic cells, with long cytoplasmic processes and lacking distinct phagosomes, were concentrated in the lymphocyte-rich area. HLA-DR alpha-chain, CD83, and CD86 mRNAs from HLA-DR+ dendritic cells, and CD28 mRNA from CD28+ T-cells were up-regulated in lymphocyte-rich area. Scanning electron microscopy demonstrated that the density of gold particles on dendritic cells was higher than that on HLA-DR+ macrophages. These results suggest that dendritic cells in radicular granulomas are associated with local defense reactions as stronger antigen-presenting cells, as compared with macrophages.

scholarly journals Acquired Protective Immunity in Atlantic Salmon Salmo salar against the Myxozoan Kudoa thyrsites Involves Induction of MHIIβ+ CD83+ Antigen-Presenting Cells

2017 ◽  
Vol 86 (1) ◽  
Author(s):  
Laura M. Braden ◽  
Karina J. Rasmussen ◽  
Sara L. Purcell ◽  
Lauren Ellis ◽  
Amelia Mahony ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
Atlantic Salmon ◽  
Protective Immunity ◽  
Antigen Presenting Cells ◽  
Content Type ◽  
Exposed Fish ◽  
Kudoa Thyrsites ◽  
Antigen Presenting

ABSTRACTThe histozoic myxozoan parasiteKudoa thyrsitescauses postmortem myoliquefaction and is responsible for economic losses to salmon aquaculture in the Pacific Northwest. Despite its importance, little is known about the host-parasite relationship, including the host response to infection. The present work sought to characterize the immune response in Atlantic salmon during infection, recovery, and reexposure toK. thyrsites. After exposure to infective seawater, infected and uninfected smolts were sampled three times over 4,275 degree-days. Histological analysis revealed infection severity decreased over time in exposed fish, while in controls there was no evidence of infection. Following a secondary exposure of all fish, severity of infection in the controls was similar to that measured in exposed fish at the first sampling time but was significantly reduced in reexposed fish, suggesting the acquisition of protective immunity. Using immunohistochemistry, we detected a population of MHIIβ+cells in infected muscle that followed a pattern of abundance concordant with parasite prevalence. Infiltration of these cells into infected myocytes preceded destruction of the plasmodium and dissemination of myxospores. Dual labeling indicated a majority of these cells were CD83+/MHIIβ+. Using reverse transcription-quantitative PCR, we detected significant induction of cellular effectors, including macrophage/dendritic cells (mhii/cd83/mcsf), B cells (igm/igt), and cytotoxic T cells (cd8/nkl), in the musculature of infected fish. These data support a role for cellular effectors such as antigen-presenting cells (monocyte/macrophage and dendritic cells) along with B and T cells in the acquired protective immune response of Atlantic salmon againstK. thyrsites.

scholarly journals Live-Cell Microscopy Reveals That Human T Cells Primarily Respond Chemokinetically Within a CCL19 Gradient That Induces Chemotaxis in Dendritic Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Evert J. Loef ◽  
Hilary M. Sheppard ◽  
Nigel P. Birch ◽  
P. Rod Dunbar
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Dynamic Control ◽  
Human Monocyte ◽  
Lymphoid Tissues ◽  
Fluorescent Marker ◽  
Biased Random Walk ◽  
Human T Cells ◽  
Antigen Presenting ◽  
System Migration

The ability to study migratory behavior of immune cells is crucial to understanding the dynamic control of the immune system. Migration induced by chemokines is often assumed to be directional (chemotaxis), yet commonly used end-point migration assays are confounded by detecting increased cell migration that lacks directionality (chemokinesis). To distinguish between chemotaxis and chemokinesis we used the classic “under-agarose assay” in combination with video-microscopy to monitor migration of CCR7+ human monocyte-derived dendritic cells and T cells in response to a concentration gradient of CCL19. Formation of the gradients was visualized with a fluorescent marker and lasted several hours. Monocyte-derived dendritic cells migrated chemotactically towards the CCL19 gradient. In contrast, T cells exhibited a biased random walk that was largely driven by increased exploratory chemokinesis towards CCL19. This dominance of chemokinesis over chemotaxis in T cells is consistent with CCR7 ligation optimizing T cell scanning of antigen-presenting cells in lymphoid tissues.

scholarly journals Tumor-Infiltrating Dendritic Cells Are Potent Antigen-Presenting Cells Able to Activate T Cells and Mediate Tumor Rejection

2005 ◽  
Vol 176 (1) ◽  
pp. 61-67 ◽  
Author(s):  
Olivier Preynat-Seauve ◽  
Prisca Schuler ◽  
Emmanuel Contassot ◽  
Friedrich Beermann ◽  
Bertrand Huard ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Antigen Presenting Cells ◽  
Tumor Rejection ◽  
Antigen Presenting

Generation of CMV-Specific T-Lymphocytes for Adoptive Immunotherapy: A Comparison of Artificial Antigen-Presenting Cells and Autologous Dendritic Cells Pulsed with CMV-pp65 Protein-Spanning Pentadecapeptide Pools.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5546-5546
Author(s):  
Wouter J.W. Kollen ◽  
Deepa Trivedi ◽  
Matthias Stephan ◽  
Michel Sadelain ◽  
Richard J. O’Reilly
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Adoptive Immunotherapy ◽  
Antigen Presenting Cells ◽  
Hla Class I ◽  
Treatment And Prevention ◽  
Endogenous Protein ◽  
Artificial Antigen ◽  
Time Required ◽  
Antigen Presenting

Abstract Adoptive transfer of virus-specific T-cells constitutes a promising approach for the treatment and prevention of cytomegalovirus (CMV) infections complicating allogeneic HSC transplants. Current strategies employing peptide-pulsed donor-derived dendritic cells (DCs) for antigen presentation are effective, but limited by availability of adequate numbers of DCs and the time required for their generation. We established a series of immediately accessible, replenishable, artificial antigen-presenting cells (AAPCs), consisting of mouse 3T3 cells transduced to express human B7.1, LFA-3, ICAM-1, β2-microglobulin and one HLA class I allele (Papanicolaou et al., Blood 2003). We then compared yields of CMV-peptide-specific T-cells when T-cells from HLA A0201 seropositive donors were sensitized with autologous DCs or HLA A0201 AAPCs loaded with a known HLA A0201-binding immunogenic nonamer of CMV-pp65 (NLVPMVATV) or a pool of pentadecapeptides spanning CMV-pp65, which included the 15-mer No. 123 (AGILARNLVPMVATV) containing this epitope. Peptide loading was performed in the presence or absence of serum in order to distinguish peptide editing mediated by ectopeptidases in the serum or expressed by the different APCs. Results from repeated experiments employing three HLA A0201 CMV-seropositive donors demonstrated that the yields of epitope-specific T-cells following 14–28 day sensitization with AAPCs loaded with the NLVPMVATV nonamer consistently exceeded those generated in response to peptide-loaded autologous DCs, as assessed by enumerating peptide-HLA A0201 tetramer-binding and peptide-specific IFN-γ producing T cells. High and selective yields of NLV-specific T-cells were obtained when the T-cells were sensitized with AAPCs or DCs loaded with the CMV-pp65-spanning pool of 15-mers in the presence or absence of serum suggesting that ectopeptidases expressed on the DCs and AAPCs appropriately clip and edit the 15-mers after binding to HLA A0201. Even higher yields were achieved when the T-cells were sensitized with AAPCs transduced to express the full length CMV-pp65 protein, confirming the potential of the mouse-derived AAPCs to process this protein and load immunogenic epitopes on HLA A0201. T-cells generated in response to peptide-loaded or transduced AAPCs also specifically lysed nonamer-loaded HLA A0201 expressing targets. Taken together, these studies indicate that mouse-derived AAPCs can efficiently process endogenous protein and edit exogenous 15-mer peptides for binding and presentation by the single expressed HLA allele. Use of these AAPCs loaded with overlapping peptides or transduced to express an immunogenic protein may thus provide advantages in terms of immunogenicity, immediate accessibility and broad applicability for rapid production of antigen-specific T-cells for adoptive immunotherapy.

Recipient Inflammation That Increases Alloimmunization Also Enhances Consumption of Transfused RBCs by Dendritic Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 23-23
Author(s):  
Jeanne E. Hendrickson ◽  
John D. Roback ◽  
Christopher D. Hillyer ◽  
James C. Zimring
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
B Cells ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Antigen Presenting Cells ◽  
Poly I:C ◽  
Splenic Macrophages ◽  
Antigen Presenting

Background: Although much is known about the structure and immunogenicity of red blood cell (RBC) antigens, little is known about their processing and presentation by antigen presenting cells (APC). Red blood cells are a unique immunogen, in that they are given intravenously, without inflammation, and typically don’t enter peripheral tissues and lymphatics. Unlike pathogens, which cause an immune response in the majority of patients, only a small minority of chronically transfused patients develop alloantibodies to RBC antigens. In a murine model of RBC transfusion, we have previously reported that recipient inflammation, induced by Poly (I:C) (a double-stranded RNA that mimics viral inflammation), significantly enhances alloimmunization to RBC antigens. In this report, we explore the role of antigen presenting cells in the immune response to antigens on transfused RBCs, in an uninflammed state as well as in the presence of Poly (I:C). Methods: 3, 3-dihexadecyloxacarbocyanine perchlorate (DiO) was used as a fluorescent RBC label. Labeled RBCs were transfused into C57BL/6 recipient mice, in the absence or presence of inflammation with poly (I:C). 24 hours post-transfusion, APCs were analyzed in the spleen, liver, and lymph nodes. Macrophages (F4/80+) and dendritic cells (DC) (CD11c+) were gated on by flow cytometry, as were T cells (CD3+), B cells (CD19+) and RBCs (Terr 119+). RBC consumption was assessed by measuring DiO fluorescence in these cell populations. Results: In the absence of inflammation, the majority of RBCs are consumed by macrophages in the spleen, with 3 fold less consumption by liver macrophages and no consumption by lymph node macrophages. Both splenic and liver DCs consume 3 fold fewer RBCs than splenic macrophages. Recipient inflammation with Poly (I:C) alters this pattern, with a significant increase in consumption by both splenic and liver DCs and a decrease in consumption by splenic macrophages. As a negative control, no RBC consumption was seen after gating on non-phagocytic T cells or B cells. Likewise, measures of RBC consumption were not an artifact of RBC sticking to the APC surface, as staining for TER119 was negative. Discussion: Red blood cells are a unique immunogen, in that they circulate for many days, don’t enter lymphatics, and often don’t cause a detectable alloantibody response. These studies demonstrate that recipient inflammation with Poly (I:C), which we have previously reported enhances alloimmunization to transfused RBCs, significantly increases DC consumption of transfused RBCs. As DCs are typically considered to be more potent APCs than macrophages, and as we have previously shown that Poly (I:C) signficantly induces co-stimulatory molecule expression on DCs, these findings provide one potential mechanism by which inflammation enhances RBC alloimmunization. Ongoing studies are directly assessing the relative potency of these different APCs in their ability to activate CD4+ T cells specific for RBC antigens.

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