Search PubMed⌕ Search

Biomedical subjects

A Vink

Publications and source records attributed to A Vink.

At least 37 records · Page 2Linked to original sources
PubMed1994

Thymic lymphomas in interleukin 9 transgenic mice.

Transgenic mice overexpressing the interleukin 9 gene were generated to study the biological activity of this cytokine in vivo. Although no major histological or morphological modifications of the lymphoid system were observed in most animals, approximately 7% of transgenic mice developed thymic lymphomas at the age of 3-9 months. The tumor cells, which were clonal, with unique T cell rearrangements, were double positive for the expression of CD4 and CD8. The need for additional transforming events, suggested by the low incidence of spontaneous tumors, was further indicated by the high susceptibility of the transgenic animals to injections of low doses of N-methyl-N-nitrosourea, a chemical carcinogen with a thymic tropism. Expression of interleukin 9 was required for optimal tumor growth in vivo, as one of the tumors studied, which had lost the transgene, was much more efficiently transplanted into transgenic than in normal mice. Moreover, the in vitro proliferative activity of interleukin 9 on cell lines derived from such transgene-negative tumors suggests that an autocrine loop mediates the proliferation of these cells in vivo. Taken together, these results indicate that dysregulated IL-9 expression could be involved in the development of some T cell malignancies.

Animals↗
PubMed1993

Interleukin-9 stimulates in vitro growth of mouse thymic lymphomas.

The ability of interleukin (IL)-9 to stimulate the in vitro proliferation of freshly collected mouse thymic lymphoma cells was tested on a panel of 45 tumors, induced by N-methyl-N-nitrosourea (MNU) or by X-ray irradiation. IL-9 significantly stimulated the proliferation of 26 of these tumors. Out of 11 other factors tested, only IL-2, IL-4 and IL-7 showed similar activities. In addition to the responses to IL-9 alone, a potent synergy was often observed between IL-9 and IL-2 for MNU-induced tumors. Synergies between IL-9 and IL-7 or IL-9 and IL-4 were also observed but less frequently. The growth-promoting activity of IL-9 and the synergistic activities of IL-2 and IL-9 for thymic lymphoma cells were confirmed with cell lines established from the fresh tumors.

Animals↗
PubMed1993

Interleukin-9.

Explore the source record for details and available documents.

Amino Acid Sequence↗
PubMed1993

Interleukin-9.

Explore the source record for details and available documents.

Amino Acid Sequence↗
PubMed1992

Limited involvement of interleukin-6 in the pathogenesis of lethal septic shock as revealed by the effect of monoclonal antibodies against interleukin-6 or its receptor in various murine models.

Several studies in human patients and in laboratory animals have revealed a correlation between serum interleukin (IL)-6 levels and outcome in clinical sepsis and in related animal models, respectively. In the present study, two monoclonal antibodies were used to investigate the contribution of IL-6 in the lethal action of tumor necrosis factor (TNF) and of lipopolysaccharide (LPS) in mice. We studied the potential protective properties of an anti-murine (m) IL-6 antibody and of an anti-mIL-6 receptor antibody. In controlled experiments, we observed that both monoclonal antibodies conferred a dose-dependent protection to a lethal dose of mTNF. Detailed studies with the monoclonal antibodies indicate, however, that protection was no longer observed when the mTNF dose was slightly higher than the lethal dose. Likewise, the anti-IL-6 monoclonal antibody protected against injections of LPS at a lethal-dose concentration, but here too failed to protect against higher doses of LPS. The anti-IL-6 monoclonal antibody was unable to protect against mTNF in mice sensitized by galactosamine, the corticoid receptor antagonist RU38486 or human (h) IL-1 beta. Protection did not correlate with the serum concentrations of IL-6. Finally, we demonstrate that hIL-6 injection did not change the sensitivity of mice towards mTNF. We conclude that, although IL-6 levels may be of value as a marker for the outcome in septic shock, this cytokine contributes only marginally in the pathogenesis leading to death. The small, but real, contribution of IL-6 in some situations might be due to its ability to up-regulate the level of TNF receptors.

Animals↗
PubMed1990

Mouse plasmacytoma growth in vivo: enhancement by interleukin 6 (IL-6) and inhibition by antibodies directed against IL-6 or its receptor.

Murine plasmacytomas show a striking dependence on interleukin 6 (IL-6) for their growth in vitro. Here, we present evidence suggesting that IL-6 also plays an essential role in the in vivo development of these tumors. This conclusion is based on the finding that the tumorigenicity of an IL-6-dependent plasmacytoma cell line was increased approximately 100-fold on transfection with an IL-6 expression vector, whereas it was inhibited in animals treated with monoclonal antibodies capable of blocking the binding of IL-6 to its receptor. Injection of these antibodies 1 d before tumor challenge protected greater than 50% of the mice and retarded tumor growth in all animals. Tumors arising in antibody-treated mice retained their IL-6 dependence in vitro, suggesting that the level of protection could be improved if stronger IL-6 antagonists were available.

Animals↗
PubMed1990

Accessory factors involved in murine T cell activation. Distinct roles of interleukin 6, interleukin 1 and tumor necrosis factor.

Interleukin (IL) 6 was compared to other macrophage-derived products for its capacity to support the proliferation of accessory cell-depleted T cells. Monoclonal anti-IL6 antibodies were found to inhibit completely the "accessory activity" of macrophage supernatants, thus demonstrating the central role played by IL6 in T cell activation. IL6 was apparently more critical for initiating than in maintaining T cell proliferation because anti-IL6 antibodies lost all inhibitory activity when added late to the culture. Moreover, IL6 was not the only accessory factor required for optimal T cell proliferation. Using low-density cultures to minimize the number of contaminating accessory cells, we found that significant proliferation of CD4 cells was obtained only in the presence of both IL6 and IL1. In contrast, with CD8 cells substantial proliferation was obtained with IL6 alone. This response could, however, be enhanced by IL1. Tumor necrosis factor (TNF) and granulocyte/macrophage colony-stimulating factor showed no activity in these assays. The concentrations of IL1 and of IL6 required to support optimal proliferation were 10 pg/ml and 1 ng/ml, respectively. Analysis of the mechanisms underlying T cell activation by IL1 and IL6 indicated that both cytokines were required for optimal production of IL2 but that IL6 alone was sufficient to confer IL2 responsiveness. For CD8 cells, this effect was observed with doses of IL6 about 100 times lower than those required for the induction of IL2 secretion (0.001 vs. 0.1 ng/ml). TNF, which was not capable of inducing IL2 secretion, was also found to induce IL2 responsiveness but only at a concentration approximately equal to 1000 times higher than that of IL6. In accordance with these observations, IL6 and to a lesser extent TNF were found to enhance IL2R expression by CD8 cells. Interestingly, this enhancing effect was totally dependent on the presence of IL2.

Animals↗
PubMed1989

Accessory signals in murine cytolytic T cell responses. Dual requirement for IL-1 and IL-6.

We have examined the nature of the accessory factors required for the development of primary murine CTL in accessory cell-depleted allogeneic mixed lymphocyte cultures. None of the known macrophage-derived factors was active by itself but the combination of IL-1 and IL-6 induced cytolytic responses equivalent to those of unfractionated cultures. Experiments with purified T cell subsets and antibodies blocking the action of IL-2 and IL-4 demonstrated that IL-1 and IL-6 acted directly on CD8+ cells capable of growth factor production. Analysis of the respective roles of IL-1 and IL-6 indicated that IL-6 acts before IL-1 and is capable apparently by itself to induce responsiveness to IL-2. By contrast, production of IL-2 required the additional presence of IL-1.

Animals↗
PubMed1989

Mouse IL-6. A hybridoma growth factor with multiple effects on normal B and T cells.

The effects of IL-6 on plasmacytomas and on normal B and T cells were examined. Evidence was presented to indicate that, in the mouse, IL-6 not only supports the growth of plasmacytomas in vitro, but also that it significantly enhances tumor progression in vivo. Analysis of the response of normal mouse B cells to IL-6 revealed the existence of a unique synergy between IL-6 and IL-1. The results obtained with T cells also highlighted the remarkable effects of the IL-1-IL-6 combination. In several experimental systems, including the generation of allogeneic cytolytic T cell responses, it appeared that accessory cells could be completely replaced by IL-1 and IL-6, whereas either cytokine used by itself was completely inactive. Analysis of the mode of action of IL-6 in T cell activation demonstrated the existence of two distinct mechanisms: induction of IL-2 biosynthesis and enhancement of T cell responsiveness to IL-2 and IL-4. Finally, it was reported that IL-6 is essential only during the early phases of T cell activation, thus indicating as far as T cells are concerned that IL-6 must be considered as a competence factor.

Animals↗
PubMed1988

Virally induced modulation of murine IgG antibody subclasses.

The isotypic distribution of murine IgG was examined after infection with several viruses. The results indicate that when a hypergammaglobulinemia was induced by the infection, it was restricted to the IgG2a and, to a lesser extent, to the IgG2b subclasses. In addition, when mice were infected with some viruses concomitantly with the immunization with a soluble protein antigen, a modification in the isotypic distribution of antiprotein antibodies was observed, with a preferential production of IgG2a. These observations indicate that viral infections can actively influence the switch of Igs and selectively stimulate the production of the IgG2a subclass.

Animals↗
PubMed1988

B cell growth and differentiation activity of interleukin-HP1 and related murine plasmacytoma growth factors. Synergy with interleukin 1.

It was recently shown that T cells, macrophages and fibroblasts produce growth factors for B cell hybridomas and plasmacytomas. These factors were subsequently identified as members of a new family of cytokines on the basis of NH2-terminal amino acid sequence analyses. Using T cell-derived interleukin-HP1 (HP1), purified to homogeneity, as the prototype of this family, we examined the effects of these molecules in conventional polyclonal B cell activation assays with anti-immunoglobulin antibodies or dextran sulfate as co-stimulators. In the absence of other cytokines, the only significant effect of HP1 was to stimulate moderately the proliferation of anti-immunoglobulin-activated B cells. By contrast, in conjunction with interleukin 1, HP1 became a major growth and differentiation factor not only for B cells activated with anti-immunoglobulin antibodies but also for dextran sulfate-stimulated and even for unstimulated B cells. In fact, with respect to cell proliferation or IgM synthesis, the IL 1-HP1 combination proved to be equivalent to B cell stimulatory factors like IL 4 or IL 5. This B cell stimulatory activity was not due to the presence of a contaminant in the HP1 preparation because it was also observed with purified plasmacytoma growth factors derived from macrophages and fibroblasts, and could be inhibited by a monoclonal anti-HP1 antibody.

Animals↗
PubMed1987

Identification of an interleukin HP1-like plasmacytoma growth factor produced by L cells in response to viral infection.

We have recently purified and partially sequenced a new T cell-derived lymphokine with growth factor activity for B cell hybridomas and plasmacytomas, which we named interleukin HP1 (HP1). Here we show that, in response to viral infection or after treatment with poly(rI).poly(rC), L cells produce a factor that is capable of supporting the in vitro growth and survival of HP1-dependent cell lines. Serologic and structural evidence is presented in favor of the identity between the fibroblast factor and HP1, demonstrating that non-T cells can make HP1-related molecules.

Animals↗
PubMed1987

Interleukin-HP1, a T cell-derived hybridoma growth factor that supports the in vitro growth of murine plasmacytomas.

We have recently described the purification and NH2-terminal amino acid sequence of a T cell-derived hybridoma growth factor that was provisionally designated interleukin-HP1 (IL-HP1). Here we report that a T cell supernatant containing high titers of this hybridoma growth factor considerably facilitated the establishment of primary cultures of murine plasmacytomas. Most plasmacytoma cell lines derived from such cultures remained permanently dependent on IL-HP1-containing T cell supernatant for both survival and growth in vitro. These cell lines, however, retained their ability to form tumors in irradiated pristane-treated mice. Analytical fractionation of a T cell supernatant rich in IL-HP1 by either gel filtration, isoelectric focusing, or reversed-phase HPLC revealed the existence of only one plasmacytoma growth factor activity that strictly copurified with IL-HP1, strongly suggesting the identity of both factors. This conclusion was further supported by the finding that IL-HP1 purified to homogeneity supported the growth of both B cell hybridomas and plasmacytomas. For half-maximal growth, plasmacytomas, however, required a concentration of IL-HP1 of approximately 30 pM, which is approximately 200 times higher than that required by B cell hybridomas. A clear difference in the specificity of IL-HP1 and B cell stimulatory factor 1 (BSF-1) was demonstrated by the finding that IL-HP1-dependent plasmacytomas did not survive in the presence of BSF-1, whereas helper T cell lines that proliferated in the presence of BSF-1 failed to respond to IL-HP1.

Animals↗
PubMed1987

Identification of the human 26-kD protein, interferon beta 2 (IFN-beta 2), as a B cell hybridoma/plasmacytoma growth factor induced by interleukin 1 and tumor necrosis factor.

A factor that promotes the growth of certain B cell hybridomas and of plasmacytomas is shown to be produced by normal human fibroblasts and by a line of human osteosarcoma cells (MG-63) after treatment with IL-1 or TNF. The hybridoma-plasmacytoma growth factor (HPGF) is identified with a 26 kD protein whose mRNA was previously shown to be induced in the same cells by the same inducers. First, poly(A)-rich RNA extracted from IL-1-treated cells could be enriched in HPGF-mRNA content by hybridization to 26 kD cDNA. Second, MG-63-derived HPGF purified to electrophoretic homogeneity was subjected to amino acid sequence analysis, whereby the NH2-terminal sequence was found to match the nucleotide sequence of a 26 kD cDNA clone.

Amino Acid Sequence↗