Interferon response factor-3 promotes the pro-Th2 activity of mouse myeloid CD11b+ dendritic cells
Janss, Thibaut ; Mesnil, Claire ; Pirottin, Dimitri et al
in European Journal of Immunology (in press)Detailed reference viewed: 29 (14 ULg)
Natural killer and dendritic cells collaborate in the immune response induced by the vaccine against uterine cervical cancer.
Langers, Inge ; ; et al
in European journal of immunology (2014), 44
Virus-like particles (VLPs) of human papillomavirus (HPV) are used as a vaccine against HPV-induced cancer, and recently we have shown that these VLPs are able to activate natural killer (NK) cells. Since ... [more ▼]
Virus-like particles (VLPs) of human papillomavirus (HPV) are used as a vaccine against HPV-induced cancer, and recently we have shown that these VLPs are able to activate natural killer (NK) cells. Since NK cells collaborate with dendritic cells (DCs) to induce an immune response against viral infections and tumors, we studied the impact of this crosstalk in the context of HPV vaccination. NK cells in the presence of HPV-VLPs enhanced DC maturation as shown by an upregulation of CD86 and HLA-DR and an increased production of IL-12p70, but not of the immunosuppressive cytokine IL-10. This activation was bi-directional. Indeed, in the presence of HPV-VLPs, DCs further activated NK cells by inducing the upregulation of cell surface activation markers (CD69 and HLA-DR). The function of NK cells was also improved as shown by an increase in IFN-gamma secretion and cytotoxic activity against an HPV+ cell line. This crosstalk between NK cells and DCs needed CD40 interaction and IL-12p70 secretion, whereas NKG2D was not implicated. Our results provide insight into how VLPs interact with innate immune cells and how NK cells and DCs play a role in the immune response induced by this vaccine agent. This article is protected by copyright. All rights reserved. [less ▲]Detailed reference viewed: 93 (12 ULg)
Antigen presenting cell-derived IL-6 restricts Th2-cell differentiation.
; ; et al
in European Journal of Immunology (2014), 44(11), 3252-62
The identification of DC-derived signals orchestrating activation of Th1 and Th17 immune responses has advanced our understanding on how these inflammatory responses develop. However, whether specific ... [more ▼]
The identification of DC-derived signals orchestrating activation of Th1 and Th17 immune responses has advanced our understanding on how these inflammatory responses develop. However, whether specific signals delivered by DCs also participate in the regulation of Th2 immune responses remains largely unknown. In this study, we show that administration of antigen-loaded, IL-6-deficient DCs to naive mice induced an exacerbated Th2 response, characterized by the differentiation of GATA-3-expressing T lymphocytes secreting high levels of IL-4, IL-5, and IL-13. Coinjection of wild type and IL-6-deficient bone marrow-derived dendritic cells (BMDCs) confirmed that IL-6 exerted a dominant, negative influence on Th2-cell development. This finding was confirmed in vitro, where exogenously added IL-6 was found to limit IL-4-induced Th2-cell differentiation. iNKT cells were required for optimal Th2-cell differentiation in vivo although their activation occurred independently of IL-6 secretion by the BMDCs. Collectively, these observations identify IL-6 secretion as a major, unsuspected, mechanism whereby DCs control the magnitude of Th2 immunity. [less ▲]Detailed reference viewed: 11 (1 ULg)
Human papillomavirus entry into NK cells requires CD16 expression and triggers cytotoxic activity and cytokine secretion.
Renoux, Virginie ; Bisig, Bettina ; Langers, Inge et al
in European journal of immunology (2011), 41(11), 3240-3252
Human papillomavirus (HPV) infections account for more than 50% of infection-linked cancers in women worldwide. The immune system controls, at least partially, viral infection and around 90% of HPV ... [more ▼]
Human papillomavirus (HPV) infections account for more than 50% of infection-linked cancers in women worldwide. The immune system controls, at least partially, viral infection and around 90% of HPV-infected women clear the virus within two years. However, it remains unclear which immune cells are implicated in this process and no study has evaluated the direct interaction between HPVs and NK cells, a key player in host resistance to viruses and tumors. We demonstrated an NK cell infiltration in HPV-associated pre-neoplastic cervical lesions. Since HPVs cannot grow in vitro, virus-like particles (VLPs) were used as a model for studying the NK cell response against the virus. Interestingly, NK cells displayed higher cytotoxic activity and cytokine production (TNF-alpha and IFN-gamma) in the presence of HPV-VLPs. Using flow cytometry and microscopy we observed that NK cell stimulation was linked to rapid VLP entry into these cells by macropinocytosis. Using CD16(+) and CD16(-) NK cell lines and a CD16-blocking antibody, we demonstrated that CD16 is necessary for HPV-VLP internalization, as well as for degranulation and cytokine production. Thus, we show for the first time that NK cells interact with HPVs and can participate in the immune response against HPV-induced lesions. [less ▲]Detailed reference viewed: 146 (47 ULg)
ADAM-8, a metalloproteinase, drives acute allergen-induced airway inflammation
Paulissen, Geneviève ; Rocks, Natacha ; Guéders, Maud et al
in European Journal of Immunology (2011), 41(2), 380-91
Asthma is a complex disease linked to various pathophysiological events including the activity of proteinases. The multifunctional A Disintegrin And Metalloproteinases (ADAMs) displaying the ability to ... [more ▼]
Asthma is a complex disease linked to various pathophysiological events including the activity of proteinases. The multifunctional A Disintegrin And Metalloproteinases (ADAMs) displaying the ability to cleave membrane-bound mediators or cytokines appear to be key mediators in various inflammatory processes. In the present study, we have investigated ADAM-8 expression and production in a mouse model of allergen-induced airway inflammation. In allergen-exposed animals, increased expression of ADAM-8 was found in the lung parenchyma and in dendritic cells purified from the lungs. The potential role of ADAM-8 in the development of allergen-induced airway inflammation was further investigated by the use of an anti-ADAM-8 antibody and ADAM-8 knock-out animals. We observed a decrease in allergen-induced acute inflammation both in BALF and the peribronchial area in anti-ADAM-8 antibody-treated mice and in ADAM-8 deficient mice (ADAM-8-/-) after allergen exposure. ADAM-8 depletion led to a significant decrease of the CD11c+ lung dendritic cells. We also report lower levels of CCL11 and CCL22 production in antibody-treated mice and ADAM-8-/- mice that might be explained by decreased eosinophilic inflammation and lower numbers of dendritic cells, respectively. In conclusion, ADAM-8 appears to favour allergen-induced acute airway inflammation by promoting dendritic cell recruitment and CCL11 and CCL22 production. [less ▲]Detailed reference viewed: 207 (39 ULg)
The L1 major capsid protein of HPV16 differentially modulates APC trafficking according to the vaccination or natural infection context.
Herman, Ludivine ; Hubert, Pascale ; Herfs, Michael et al
in European Journal of Immunology (2010), 40(11), 3075-84
Human papillomavirus (HPV) infection, particularly type 16, is causally associated with cancer of the uterine cervix. The progression of cervical lesions suggests that viral antigens are not adequately ... [more ▼]
Human papillomavirus (HPV) infection, particularly type 16, is causally associated with cancer of the uterine cervix. The progression of cervical lesions suggests that viral antigens are not adequately presented to the immune system. The aim of this study was to determine whether HPV16 viral particles can influence the trafficking of human DC/Langerhans cells (LC), either by direct interactions with DC or following incubation with human normal keratinocytes that are in close contact with LC in the squamous epithelium. We first demonstrated that HPV16 L1 major capsid protein, when self-assembled into virus-like particles (VLP), is able to induce in DC an over-expression of CXC receptor 4 (CXCR4) via the activation of the NF-kappaB signaling pathway and to enhance DC motility in the presence of CXCL12, suggesting an ability to migrate towards lymph nodes. We also showed that conditioned media of HPV16 VLP-treated keratinocytes induce a lower LC migration than those from untreated keratinocytes and that prostaglandin E2 (PGE(2)), detected in HPV16 VLP-treated keratinocyte supernatants, may reduce LC recruitment into the squamous epithelium. Taken together, our data demonstrate that HPV16 VLP may differentially regulate the immune protective response according to their target cells. [less ▲]Detailed reference viewed: 38 (10 ULg)
Control of Schistosoma mansoni egg-induced inflammation by IL-4-responsive CD4+CD25−CD103+Foxp3− cells is IL-10-dependent
Dewals, Benjamin G ; ; et al
in European Journal of Immunology (2010), 40
Host protection to helminth infection requires IL-4Rα signalling and the establishment of finely regulated Th2 responses. In the present study, the role of IL-4Rα-responsive T cells in Schistosoma mansoni ... [more ▼]
Host protection to helminth infection requires IL-4Rα signalling and the establishment of finely regulated Th2 responses. In the present study, the role of IL-4Rα-responsive T cells in Schistosoma mansoni egg-induced inflammation was investigated. Egg-induced inflammation in IL-4Rα-responsive BALB/c mice was accompanied with Th2-biased responses, whereas T cell-specific IL-4R-deficient BALB/c mice (iLckcreIl4ra−/lox) developed Th1-biased responses with heightened inflammation. The proportion of Foxp3+ Tregs in the draining lymph node of control mice did not correlate with the control of inflammation and was reduced in comparison to T cell-specific IL-4R-deficient mice. This was due to IL-4-mediated inhibition of CD4+Foxp3+ Tregs conversion, demonstrated in adoptively transferred Rag2−/− mice. Interestingly, reduced footpad swelling in Il4ra−/lox mice was associated with the induction of IL-4 and IL-10-secreting CD4+CD25−CD103+Foxp3− cells, confirmed in S. mansoni infection studies. Transfer of IL-4Rα-responsive CD4+CD25−CD103+ cells, but not CD4+CD25high or CD4+CD25−CD103− cells, controlled inflammation in iLckcreIl4ra−/lox mice. It finally turned out that the control of inflammation depended on IL-10, as transferred CD4+CD25−CD103+ cells from IL-10-deficient mice were not able to effectively downregulate inflammation. Together, these results demonstrate that IL-4 signalling in T cells inhibits Foxp3+ Tregs in vivo and promotes CD4+CD25−CD103+Foxp3− cells that control S. mansoni egg-induced inflammation via IL-10. [less ▲]Detailed reference viewed: 48 (10 ULg)
Interaction between Natural Killer and dendritic cells in the presence of vaccine agent of uterine cervical cancer
Renoux, Virginie ; Reschner, Anca ; Langers, Inge et al
in European Journal of Immunology (2009), 39Detailed reference viewed: 26 (11 ULg)
DiC14-amidine cationic liposomes stimulate myeloid dendritic cells through Toll-like receptor 4.
; ; et al
in European journal of immunology (2008), 38(5), 1351-7
DiC14-amidine cationic liposomes were recently shown to promote Th1 responses when mixed with allergen. To further define the mode of action of diC14-amidine as potential vaccine adjuvant, we ... [more ▼]
DiC14-amidine cationic liposomes were recently shown to promote Th1 responses when mixed with allergen. To further define the mode of action of diC14-amidine as potential vaccine adjuvant, we characterized its effects on mouse and human myeloid dendritic cells (DC). First, we observed that, as compared with two other cationic liposomes, only diC14-amidine liposomes induced the production of IL-12p40 and TNF-alpha by mouse bone marrow-derived DC. DiC14-amidine liposomes also activated human DC, as shown by synthesis of IL-12p40 and TNF-alpha, accumulation of IL-6, IFN-beta and CXCL10 mRNA, and up-regulation of membrane expression of CD80 and CD86. DC stimulation by diC14-amidine liposomes was associated with activation of NF-kappaB, ERK1/2, JNK and p38 MAP kinases. Finally, we demonstrated in mouse and human cells that diC14-amidine liposomes use Toll-like receptor 4 to elicit both MyD88-dependent and Toll/IL-1R-containing adaptor inducing interferon IFN-beta (TRIF)-dependent responses. [less ▲]Detailed reference viewed: 10 (0 ULg)
Prostaglandin D2 affects the differentiation and functions of human dendritic cells: impact on the T cell response.
; ; et al
in European Journal of Immunology (2005), 35(5), 1491-1500
The local environment in which dendritic cells (DC) differentiate is important for the acquisition of their immunostimulatory properties. Since prostaglandin D(2) (PGD(2)), a major prostanoid produced ... [more ▼]
The local environment in which dendritic cells (DC) differentiate is important for the acquisition of their immunostimulatory properties. Since prostaglandin D(2) (PGD(2)), a major prostanoid produced during inflammatory reactions, is involved in the control of immune responses, its effect on the differentiation and functions of human monocyte-derived dendritic cells (MDDC) was studied. We show that DC differentiated in the presence of PGD(2) (PG/DC) have an unusual phenotype, with modifications in the expression of molecules involved in antigen (Ag) capture and presentation, leading to higher endocytic and Ag-processing activities. However, under conditions that necessitated Ag processing and presentation, PG/DC have an impaired ability to stimulate naive T cells, whereas superAg-pulsed DC efficiently promote their proliferation. Upon lipopolysaccharide or TNF-alpha/IL-1beta stimulation, PG/DC phenotypically mature but produce abnormal amounts of immunoregulatory cytokines (decreased IL-12p70/IL-10 ratio). Moreover, mature PG/DC fail to up-regulate the chemokine receptor CCR7 and show an impaired migration towards its ligand CCL19. Finally, PG/DC favor the differentiation of naive T cells toward Th2 cells, an effect dependent on IL-10 and inducible costimulator ligand expression by DC. Most of the herein described effects of PGD(2) on MDDC can be reproduced, usually with a higher efficacy, with a selective D prostanoid receptor (DP)1, but not DP2, agonist. Taken as a whole, these results demonstrate that PGD(2) impacts DC differentiation and functions, and extend the concept that it exerts important roles in immunity [less ▲]Detailed reference viewed: 13 (3 ULg)
Prostaglandin D2 inhibits the production of interleukin-12 in murine dendritic cells through multiple signaling pathways.
; ; Bureau, Fabrice et al
in European Journal of Immunology (2003), 33(4), 889-898
Prostaglandin (PG) D(2), and its metabolites, are known to be important mediators during acute and chronic inflammation. However, their functions during the early phases of the immune response are poorly ... [more ▼]
Prostaglandin (PG) D(2), and its metabolites, are known to be important mediators during acute and chronic inflammation. However, their functions during the early phases of the immune response are poorly documented. In the present study, we show that PGD(2 )inhibits, in a dose-dependent manner, the CD40- and LPS-induced secretion of the Th1-driving factor IL-12 by murine splenic dendritic cells (DC), the most potent antigen-presenting cells. The inhibition of IL-12 production is mediated only in part by the cell surface G alpha s protein-coupled D prostanoid receptor (termed DP1) but not by the G alpha i protein-coupled DP receptor, DP2. We show that recruitment of DP1 in DC results in the activation of a cyclic AMP/protein kinase A pathway that is partially responsible for the inhibition of IL-12 production. We also suggest that the DP1-independent effects exerted by PGD(2) on IL-12 production may be due to the action of ist PGJ(2), but not PGF(2)alpha, metabolites. Electrophoretic mobility shift assays demonstrated that PGD(2) affects NF-kappa B activation through (the) DP1-independent pathway(s). Together these data suggest that PGD(2), by interacting with DP1 and by binding to other target cellular proteins, may regulate immune responses by affecting IL-12 production in DC [less ▲]Detailed reference viewed: 37 (1 ULg)
CD4+ T cells determine the ability of spleen cells from F1 hybrid mice to induce neonatal tolerance to alloantigens and autoimmunity in parental mice
; Schurmans, Stéphane ; et al
in European Journal of Immunology (1995), 25
Spleen cells from F1 hybrid mice injected into newborn parental mice induce a state of cytolytic unresponsiveness to the corresponding alloantigens. However, these mice develop a transient autoimmune ... [more ▼]
Spleen cells from F1 hybrid mice injected into newborn parental mice induce a state of cytolytic unresponsiveness to the corresponding alloantigens. However, these mice develop a transient autoimmune syndrome characterized by the production of multiple autoantibodies and glomerulonephritis. Previous reports indicated that the depletion of F1 donor T cells, shortly prior the injection into parental mice, does not interfere with any of these events. Here, we have explored whether the continuous absence of T cells in F1 mice influences the ability of their spleen cells to induce neonatal tolerance to alloantigens and the associated autoimmune manifestations. Our results revealed that spleen cells from athymic (BALB/c x C57BL/6) F1 hybrid (CB6F1) nu/nu mice or from euthymic CB6F1 mice depleted from birth of CD4+ T cells, but not of CD8+ T cells, are unable to induce neonatal tolerance to alloantigens and autoimmune manifestations. By contrast, the partial reconstitution of T cells in CB6F1 nu/nu mice, after the neonatal graft of a syngeneic thymus, restored the capacity of spleen cells from these mice to induce tolerance and autoimmunity when injected into newborn BALB/c mice. These results demonstrate that the functional defect of spleen cells from athymic CB6F1 nu/nu mice to induce neonatal tolerance to alloantigens is directly related to the long-term absence of mature CD4+ T cells. Interestingly, a new increase in the titers of anti-DNA Ab was observed when spleen cells from athymic CB6F1 nu/nu mice were injected into adult BALB/c mice that had been tolerized at birth with normal CB6F1 spleen cells. This finding indicates that B cells from CB6F1 nu/nu mice recover their capacity to interact with alloreactive Th2 cells when they are placed into mice having functional CD4+ T cells. These data indicate that the continuous absence of CD4+ T cells causes a reversible functional defect in F1 spleen cells that determines their inability to induce neonatal tolerance and autoimmunity [less ▲]Detailed reference viewed: 23 (5 ULg)
Anti-LFA-1 (CD11a) monoclonal antibody interferes with the induction of neonatal tolerance to alloantigens
Schurmans, Stéphane ; ; et al
in European Journal of Immunology (1994), 24
The injection of (C57BL/6 x BALB/c)F1 spleen cells into newborn BALB/c mice results in the induction of a specific cytotoxic T lymphocyte (CTL) tolerance to the alloantigens. On the contrary, alloreactive ... [more ▼]
The injection of (C57BL/6 x BALB/c)F1 spleen cells into newborn BALB/c mice results in the induction of a specific cytotoxic T lymphocyte (CTL) tolerance to the alloantigens. On the contrary, alloreactive CD4+ T cells persist in the host and are still able to activate autoreactive F1 B cells to produce autoantibodies. This state of "split tolerance" is closely associated with the development of a lupus-like autoimmune syndrome. The LFA-1 integrin plays a relevant role in homing, intercellular adhesion and tranduction of co-stimulatory signals in leukocytes. Because of the beneficial effects of anti-LFA-1 monoclonal antibodies (mAb) treatment in various models of organ transplantation and autoimmune disease, we have investigated if such a treatment could interfere with the induction of neonatal tolerance or the development of the autoimmune syndrome in F1 cell-injected newborn mice. For this purpose, BALB/c mice neonatally injected with F1 cells were treated from day 1 up to day 15 with a non-cytotoxic anti-LFA-1 (CD11a) mAb. Anti-LFA-1 mAb treatment interfered with the persistence of a stable chimerism and with the establishment of CTL tolerance, as shown by rejection of allogeneic skin grafts and F1 B cells, and by a normal in vitro CTL activity against the corresponding alloantigens. As a consequence, these mice did not develop the characteristic autoimmune features seen in close association with an effective induction of CTL tolerance to alloantigens. These results stress the importance of the interactions between LFA-1 and its ligands during the neonatal induction of tolerance to alloantigens [less ▲]Detailed reference viewed: 35 (4 ULg)
Effect of Interferon-Gamma and Tumor Necrosis Factor-Alpha on Lymphoepithelial Interactions within Thymic Nurse Cells
Defresne, Marie-Paule ; Humblet, Chantal ; et al
in European Journal of Immunology (1990), 20(2), 429-32
Isolated thymic nurse cells (TNC) represent a specialized microenvironment in vivo where thymocytes interact specifically with subcapsular epithelial cells. They are thought to play a critical role in the ... [more ▼]
Isolated thymic nurse cells (TNC) represent a specialized microenvironment in vivo where thymocytes interact specifically with subcapsular epithelial cells. They are thought to play a critical role in the process of T cell differentiation. We demonstrate that recombinant murine interferon-gamma and recombinant human tumor necrosis factor-alpha can act on these interactions: they stimulate TNC-derived epithelial cells to establish interactions with thymocytes in vitro and to form new lymphoepithelial complexes. This phenomenon is partially inhibited by anti-Ia monoclonal antibodies. Implications of these findings for normal intrathymic differentiation are discussed. [less ▲]Detailed reference viewed: 9 (0 ULg)
Spontaneous production of anti-mouse red blood cell autoantibodies is independent of the polyclonal activation in NZB mice
; ; Schurmans, Stéphane et al
in European Journal of Immunology (1990), 20
New Zealand Black (NZB) mice spontaneously develop an autoimmune hemolytic anemia together with a markedly increased production of polyclonal antibodies. The spontaneous generation of anti-mouse red blood ... [more ▼]
New Zealand Black (NZB) mice spontaneously develop an autoimmune hemolytic anemia together with a markedly increased production of polyclonal antibodies. The spontaneous generation of anti-mouse red blood cells (MRBC), anti-bromelain-treated MRBC (BrMRBC) and anti-DNA autoantibodies was compared to the polyclonal antibody formation in irradiated (800 rad) 2-month-old NZB mice reconstituted with bone marrow cells (BMC) from 2- or 10-month-old NZB mice. The injection of 10-month-old NZB BMC markedly accelerated the mortality rate in parallel with the progressive increase of anti-MRBC and anti-BrMRBC autoantibody production, but the spontaneous production of polyclonal IgM antibodies and anti-DNA autoantibodies was completely abolished down to the levels of non-autoimmune mice. In contrast, mice reconstituted with 2-month-old NZB BMC exhibited neither the acceleration of anemia nor the lack of polyclonal antibody production. These results strongly suggest that the spontaneous production of anti-MRBC autoantibodies, including anti-BrMRBC autoantibodies, in the NZB mouse occurs independently of the polyclonal B cell activation, and that they result from a specific immune stimulation, while the anti-DNA autoantibody production is a consequence of polyclonal antibody formation [less ▲]Detailed reference viewed: 22 (2 ULg)
Localization of interleukin 6 mRNA in human tonsils by in situ hybridization.
; ; Heinen, Ernst et al
in European Journal of Immunology (1989), 19(12), 2379-81
We have investigated which areas produce interleukin 6 (IL 6) in human tonsils. This growth factor is required for the terminal differentiation of B lymphocytes into plasmocytes. Using 35S-labeled IL 6 ... [more ▼]
We have investigated which areas produce interleukin 6 (IL 6) in human tonsils. This growth factor is required for the terminal differentiation of B lymphocytes into plasmocytes. Using 35S-labeled IL 6 cDNA we demonstrated IL 6 gene expression over various areas of the tonsils, with consistent exception of the follicles, by in situ hybridization. It is, therefore, proposed that B cells are stimulated during their migration out of the follicles. [less ▲]Detailed reference viewed: 17 (1 ULg)
Thrombocytopenia associated with the induction of neonatal tolerance to alloantigens: immunopathogenic mecanisms.
; ; Schurmans, Stéphane et al
in European Journal of Immunology (1989), 19
BALB/c mice rendered tolerant to alloantigens by neonatal injection of semi-allogeneic (C57BL/6 x BALB/c)F1 spleen cells develop a thrombocytopenia in association with an autoimmune lupus-like syndrome ... [more ▼]
BALB/c mice rendered tolerant to alloantigens by neonatal injection of semi-allogeneic (C57BL/6 x BALB/c)F1 spleen cells develop a thrombocytopenia in association with an autoimmune lupus-like syndrome. The possible mechanisms involved in the thrombocytopenia were investigated. The development of thrombocytopenia was first detected at 3 weeks of age coinciding with the start of the other autoimmune manifestations and was always related to a state of tolerance and B cell chimerism. There was a significant increase of megakaryocytes in bone marrow and spleens from thrombocytopenic tolerant mice and radiolabeled platelets from these mice were more rapidly eliminated from the bloodstream than normal platelets when injected into normal recipients. A significant correlation between the spleen weight and the decrease of the circulating platelets was observed, although some mice with severe thrombocytopenia had only a moderate spleen enlargement. Thrombocytopenia significantly correlates with the levels of platelet-associated IgG (PAIgG) but not with anti-single-stranded DNA antibodies or circulating immune complexes. Platelets from mice with high levels of PAIgG had a shorter life-span when injected into normal mice than those from mice with low or normal PAIgG. The possibility that PAIgG are partially due to antibodies reacting specifically with platelet membrane components was analyzed. First, F(ab')2 Ig fragments from tolerant mice were shown to bind to normal platelets, in contrast to F(ab')2 Ig fragments from normal mice. Second, some monoclonal antibodies produced by hybridomas derived from tolerant mice reacted in vitro with platelets and induced a transient thrombocytopenia after i.v. injection into normal mice. These data suggest that the thrombocytopenia observed in tolerant mice is the result of a peripheral hyperdestruction of platelets associated with (a) hypersplenism, (b) nonspecific fixation of immunoglobulins, probably as immune complexes and (c) with autoantibodies reacting specifically with platelets. It may represent an interesting model for human chronic idiopathic thrombocytopenia [less ▲]Detailed reference viewed: 18 (3 ULg)
Transfer of immune complexes from lymphocytes to follicular dendritic cells.
Heinen, Ernst ; ; et al
in European Journal of Immunology (1986), 16(2), 167-72
Antigens in the form of immune complexes are retained on the membranes of follicular dendritic cells (FDC) for long periods of time. To examine how immune complexes reach germinal centers, where FDC are ... [more ▼]
Antigens in the form of immune complexes are retained on the membranes of follicular dendritic cells (FDC) for long periods of time. To examine how immune complexes reach germinal centers, where FDC are located, we injected mice with anti-2,4-dinitrophenyl (DNP) antibodies complexed to DNP-myoglobin-coated gold particles. The distribution of the particles in spleens or draining lymph nodes was then determined with the electron microscope. The vast majority of the particles were cell bound. Shortly after injection they were phagocytized by macrophages or fixed on lymphocytes. The latter were found even in the corona of lymph follicles but not in germinal centers. Already 30 min after injection, FDC in contact with the corona were faintly positive but were negative in the center. FDC precursor cells were occasionally observed but in too small a number to account for the transport of immune complexes to the germinal centers. Twenty-four hours after injection colloidal gold particles were found in phagolysosomes of macrophages or on cytoplasmic extensions of FDC in all parts of the germinal centers. Experiments performed on isolated FDC showed that they are not only able to take up free immune complexes but are also able to adsorb immune complexes from pulsed lymphocytes. These results strengthen the idea that lymphoid cells binding immune complexes by their Fc receptors may transport these complexes inside germinal centers. [less ▲]Detailed reference viewed: 10 (0 ULg)
Isolation of follicular dendritic cells from human tonsils and adenoids. II. Immunocytochemical characterization.
Heinen, Ernst ; Lilet, Chantal ; et al
in European Journal of Immunology (1984), 14(3), 267-73
Follicular dendritic cells (FDC) are specialized cells found only within lymphoid follicles. They bind immune complexes and play a role in the presentation of antigen to follicular B cells and in the ... [more ▼]
Follicular dendritic cells (FDC) are specialized cells found only within lymphoid follicles. They bind immune complexes and play a role in the presentation of antigen to follicular B cells and in the generation of B cell memory. In the present report the isolation of FDC from human tonsils and adenoids is described. These isolated cells have an unusual spherical arrangement and enclose lymphocytes within extensions of their membranes. Their ultrastructural features are similar to those observed in situ. The reactivity of isolated FDC with a number of monoclonal antibodies was analyzed by immunofluorescence and by immunostaining (at the electron microscopic level) with colloidal gold. In keeping with the results of previous investigations on tissue sections IgM, IgG and IgA (but not IgD) can be detected on the surface of isolated FDC, as can C3b receptors and the FDC-associated antigen detected by monoclonal antibody R4/23. The immunoglobulins associated with FDC are mostly embedded in an electron-dense material. The majority of the lymphoid cells enclosed within the membrane extensions of FDC are of B cell type. These results suggest that isolated FDC may be suitable for further in vitro investigation of their role in the humoral immune response. [less ▲]Detailed reference viewed: 31 (0 ULg)