Adri Van Oudenaren | ErasmusMC Rotterdam (original) (raw)

Papers by Adri Van Oudenaren

Journal of Immunological Methods, 1994

The availability of cell lines that are transfected with IL-4, IL-5 and IFN-gamma cytokine genes ... more The availability of cell lines that are transfected with IL-4, IL-5 and IFN-gamma cytokine genes permits the prolonged in vivo delivery of functional cytokines in relatively large doses for the modulation of specific immune responses. Often the transfected cells are xenogeneic or allogeneic to the experimental animal and have to be encapsulated in such a way that no cellular response by the host will be induced. Alginate has proven to be a simple matrix for encapsulating cells under mild conditions suitable for in vivo implantation. Encapsulated cells express the transfected IL-4 gene for at least 14 days after in vivo implantation and were shown to be functional during that period by modulating ongoing IgE responses. The application of adherent growing transfected cells permits dose-response titrations and provides an easy method for local and systemic cytokine delivery. Alternatively, hybridoma cells can be encapsulated and the secreted antibody monitored in the serum. It was found that no host immune response was triggered by alginate encapsulated cells. The efficiency of treatment by encapsulated hybridoma cells was shown to be equivalent to that of injecting purified antibodies.

Mediators of Inflammation, 1994

ADJUVANTS are considered to play an important role in directing the isotype and amount of antibod... more ADJUVANTS are considered to play an important role in directing the isotype and amount of antibodies produced upon immunization by conducting the development of either Th-1 or Th-2 cells upon T-cell stimulation. This is based on the different cytokine production patterns that were observed after in vitro resttmulation of T cells isolated from mice immunized with antigen either adsorbed on alum or emulsified in complete Freund adjuvant (CFA). However, other studies suggest that primarily the type of antigen determines which isotypes are produced and to what extent. In these studies, however, IgE was not determined. Therefore, this study examined whether alum and CFA influenced the amount and/or ratio of IgG1, IgE and IgG,= produced after TNP-KLH immunization. Similar levels of IgG1, IgE and IgG2a antibodies were found upon immunization with TNP-KLH either adsorbed on alum or emulsified in CFA. Moreover, administration of IFNin combination with TNP-KLH adsorbed on alum did not increase the amount of IgG produced. IFN-T treatment resulted in an increased IL-6 and decreased IFNproduction by spleen cells upon Con A stimulation, whereas it did not change the IL-4 production in similar conditions. The presented results suggest that upon immunization with TNP-KLH high IL-4 levels are produced, resulting in an antibody response that is dominated by IgG, independent of the adjuvant employed. The IL-4 inducing property of TNP-KLH is substantiated by the finding that repeated immunization of mice with TNP-KI, without adjuvant, increases the serum total IgE level. The presented data suggest that the carrier part of TNP-KLH preferentially results in Th-2 cell activity after which the adjuvant merely enhances the antibody responses generated.

Immunology Methods Manual, 1996

International archives of allergy and applied immunology

A comparison was made between the serum immunoglobulin (Ig) levels in H-2 compatible AKR and C3H ... more A comparison was made between the serum immunoglobulin (Ig) levels in H-2 compatible AKR and C3H mice. The IgG1 and especially the IgA level in preleukemic AKR mice was much lower than in age-matched C3H mice, while the IgM concentration was hardly different for AKR and C3H. Lethally irradiated AKR and C3H mice reconstituted with syngeneic bone marrow (BM) cells showed a return to serum Ig levels which are normal for these strains. In AKR mice reconstituted with C3H BM cells low IgA levels were observed. On the other hand, in C3H mice reconstituted with AKR BM cells high quantities of IgA appeared, showing the AKR allotype. It is concluded that the low serum IgA concentration in AKR mice is not a reflection of a genetically determined inability of the B cell line to produce IgA, but rather a manifestation of a genetically determined capability to prevent IgA synthesis.

Diabetology & Metabolic Syndrome, 2016

Recently, we reported signs of inflammation (raised IL-8, reduced miR-146a) and signs of vascular... more Recently, we reported signs of inflammation (raised IL-8, reduced miR-146a) and signs of vascular repair (raised HGF) in the serum of Ecuadorian patients with type 2 diabetes (T2D). In contrast, we found that the circulating monocytes lacked up-regulation of classical inflammatory genes (IL-1B, IL-6, and TNF) and there was even significant down-regulation of PTGS2. Notably, genes and a microRNA involved in adhesion, cell differentiation and morphology (CD9, DHRS3, PTPN7 and miR-34c-5p) were up-regulated in the T2D monocytes, suggesting a role of the anti-inflammatory cells in adhesion, vascular repair and invasion. To determine the gene expression of the vascular repair factor HGF in the circulating monocytes of patients with T2D and to investigate the relationship between HGF and the expression of the other previously tested monocyte genes and the contribution to the raised serum level of HGF. In addition, we tested the level of 6 microRNAs, which were previously found abnormal in the circulating monocytes, in the serum of the patients. A gene and microRNA expression study in monocytes and serum of 64 Ecuadorian patients with T2D (37-85 years) and 44 non-diabetic controls (32-87 years). The gene expression of HGF was significantly raised in the monocytes of the patients with T2D and associated with the expression of genes involved in adhesion, cell differentiation and morphology. HGF gene expression did not correlate with the serum level of HGF. The monocyte expression of pro-inflammatory cytokine genes was also not associated with the serum levels of these cytokines. The level of miR-574-3p was significantly decreased in the serum of the patients with T2D, and correlated in expression with the decreased well-established inflammation-regulating miR-146a. The level of the microRNAs in serum did not correlate with their expression level in monocytes. In circulating monocytes of Ecuadorian T2D patients, the microRNA and gene expression of important inflammatory/chemotactic/motility/vascular repair factors differs from the expression in serum. While monocytes show a gene expression profile compatible with an anti-inflammatory state, serum shows a molecular profile compatible with an inflammatory state. Both compartments show molecular signs of vascular repair support, i.e. up-regulated HGF levels.

Advances in Experimental Medicine and Biology

Transplantation proceedings, 1994

Scandinavian journal of gastroenterology, 1984

The course of a hepatitis B virus infection is probably determined by the cellular immune respons... more The course of a hepatitis B virus infection is probably determined by the cellular immune response of the host, which is partly regulated by the T helper and T suppressor cells. We therefore counted immunoregulatory T-cell subsets in the peripheral blood of 97 patients with various courses of hepatitis B virus infection: 23 of these patients were asymptomatic HBsAg carriers without detectable liver disease, 13 had chronic persistent hepatitis B, 19 had chronic active hepatitis B (11 HBeAg, 8 anti-HBe), 7 had chronic active hepatitis with anti-HBs or anti-HBc, and 35 were healthy controls with anti-HBs after recovery from acute hepatitis B. Peripheral blood mononuclear cells were specifically labelled with monoclonal Leu-1 (T cells), Leu-2a (T suppressor/cytotoxic cells), and Leu-3a (T helper cells) antisera and analyzed by flow cytometry. Leu-3a/Leu-2a ratios for patients with persistent virus infection did not differ from those found for patients who cleared the hepatitis virus ant...

Journal of immunology (Baltimore, Md. : 1950), 1982

Primary immunization of mice with certain thymus-independent (TI) antigens (i.e., TNP-LPS and DNP... more Primary immunization of mice with certain thymus-independent (TI) antigens (i.e., TNP-LPS and DNP-Ficoll) leads to antibody formation in the bone marrow (BM). TNP-Brucella abortus, Pneumococcus pneumoniae organisms, and alpha-(1,6) dextran, on the other hand, do not induce a BM antibody-producing plaque-forming cell (PFC) response. This paper deals with the mechanism underlying antibody formation in the BM to TNP-LPS and DNP-Ficoll. The majority of the BM-localizing PFC induced by TNP-LPS are formed within the BM from the proliferating lymphocyte pool, because this response was found to be resistant to splenectomy and sensitive to treatment with hydroxyurea (HU) before immunization. This local activation of newly formed B cells requires in addition to the antigenic signal of TNP-LPS the mitogenic signal from the lipid A component of LPS. In contrast, the BM PFC response to DNP-ficoll was reduced in splenectomized mice and resistant to HU treatment before the primary immunization. Th...

Journal of immunology (Baltimore, Md. : 1950), 1985

The frequencies of lipopolysaccharide (LPS)-reactive B cells and their antibody specificity reper... more The frequencies of lipopolysaccharide (LPS)-reactive B cells and their antibody specificity repertoire have been determined in the spleen and bone marrow (BM) of conventional (CV) and "antigen-free" C3H/HeCr mice of various ages. The antigen-free mice were germfree (GF)-raised and were fed an ultrafiltered solution of chemically defined (CD) low m.w. nutrients, and were thus devoid of exogenous antigenic stimulation. Spleen and BM cells were grown in a limiting dilution culture system that allows the growth and development of every newly formed LPS-reactive B cell into a clone of IgM-secreting cells which are capable of switching to other immunoglobulin (Ig) heavy chain isotypes (C-gene expression). The secretion of IgM and IgG1 was determined in the protein A plaque assay, whereas specific IgM antibody-secreting cells (V-gene expression) were detected in plaque assays specific for various heterologous erythrocytes and sheep red blood cells (SRBC) coupled with a number of ...

Immunology, 1987

The influence of the synthetic corticosteroid dexamethasone sodium phosphate (DEXA) upon mouse B ... more The influence of the synthetic corticosteroid dexamethasone sodium phosphate (DEXA) upon mouse B cells was studied. This was done by in vivo treatment of mice with a single or multiple injection of DEXA, and by culturing murine spleen cells and bone marrow cells in vitro in the presence of different concentrations of DEXA. The effect of DEXA on the B-cell compartment was assayed by polyclonal stimulation of the B cells by Escherichia coli lipopolysaccharide (LPS) in vitro and subsequent measurement of the Ig-secreting cell response in the protein A plaque assay. DEXA treatment could greatly reduce the number of B cells in the spleen, but the bone marrow B-cell compartment was quite resistant to DEXA. The in vitro LPS-induced IgM response of the residual B cells from both spleen and bone marrow and their capacity to switch from IgM to IgG and IgA secretion were not affected. These data indicate that DEXA can decrease the total number of B cells but not the functional capacity of the ...

Immunopharmacology

The influence of cyclophosphamide (CY) was studied on the B-cell compartment of mice. This was do... more The influence of cyclophosphamide (CY) was studied on the B-cell compartment of mice. This was done at five different levels: (a) the serum immunoglobulin (Ig) levels; (b) the numbers of 'background' Ig-secreting cells; (c) the incidence of surface Ig+ B cells; (d) the capacity of lipopolysaccharide-reactive B cells to give rise to a polyclonal IgM- and IgG-response in vitro; and (e) the capacity of long-lived memory B cells to give rise to an adoptive anti-sheep red blood cell plaque-forming cell response in vivo. A single injection of 300 mg CY/kg body weight (BW) decreased the numbers of background IgM-, IgG- and IgA-secreting cells in spleen, bone marrow and lymph nodes to minimum values of about 25% of normal at day 7. The incidence of surface Ig+ B cells also gradually decreased after CY treatment. The functional capacity of the B cells, however, was completely abolished one day after a single injection of 300 mg CY/kg BW. This was found for the lipopolysaccharide-reac...

Transplantation proceedings, 1987

Advances in Experimental Medicine and Biology, 1982

The kinetics and magnitude of the nonspecific humoral immune response was studied at the cellular... more The kinetics and magnitude of the nonspecific humoral immune response was studied at the cellular level in mice immunized with sheep erythrocytes (SRBC). Intravenous injection of the antigen evoked, in addition to a specific anti-SRBC response, a nonspecific response of all immunoglobulin (Ig) classes and subclasses. This nonspecific response peaked on day 4 or 5 after immunization, irrespective of the Ig class. The absolute number of nonspecific Ig-secreting cells induced by immunization varied with the different Ig-classes, and it was not proportional to the background level of Ig-secreting cells of the various classes. The nonspecific IgM-IgG1- and IgG2-response was 3 to 4 times as large as the antigen-specific responses of these classes. The nonspecific IgA-response, however, was many times greater.

No part of this thesis may be reproduced or transmitted in any form by any means, electronic Of m... more No part of this thesis may be reproduced or transmitted in any form by any means, electronic Of mechanical, including photocopying, recording or any information storage and retrieval system, without permission in writing from the publisher (P.A,

Transplant International Official Journal of the European Society for Organ Transplantation, 1992

Graft-versus-host disease (GVHD) is caused by donor T lymphocytes that recognize foreign antigens... more Graft-versus-host disease (GVHD) is caused by donor T lymphocytes that recognize foreign antigens on host tissues. This leads to T cell activation, which involves a cascade of events including the transcription of genes for cytokines and their receptors and the production of cytokines. One of the first cytokines to appear is interleukin 2 (IL-2). IL-2 production enhances the IL-2 receptor expression and leads to T cell proliferation. As a further step, differentation of T cells occurs, which results in the production of a certain pattern of cytokines. These cytokines influence the expression of cell surface antigens and adhesion molecules, and are able to activate other cell types such as cytotoxic T cells, macrophages and natural killer cells, which might act as effector cells in tissue destruction. Insight into the sequential expression of the various cytokines involved might enable a more effective treatment of GVHD. Therefore, we investigated the occurrence of cytokines in a murine model for acute GVHD. We addressed in particular the period early after allogeneic reconstitution.

Immunology Today, 1982

, about the role of 'natural' circulating antibodies in antibody formation and the completeness o... more , about the role of 'natural' circulating antibodies in antibody formation and the completeness of the repertoire of antigenbinding specificities as represented among the natural antibodies.