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  • 1
    Electronic Resource
    Electronic Resource
    Impaired Antigen-Specific B-Cell Response and Altered Splenic Microstructure in Mice Following Continuous Administration of IL-4 In Vivo (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 41 (1995), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The effect of long term in vivo administration of IL-4 on the induction of antigen-specific B cells, the splenic microenvironment and the yield of antigen-specific antibody producing hybridomas was studied. Immunization with DNP-KLH, followed by 12 weeks continuous IL-4 treatment resulted in increased numbers of total splenic (non-DNP) IgM and IgG AFC (antibody forming cells) on day 5 after booster, whereas the DNP-specific IgG and IgG1 AFC were reduced compared to age-matched control animals not treated with IL-4. In addition, an almost 300-fold increase in non-DNP IgE was found while the IgE anti-DNP response was minimal.When the splenic cells were used in a fusion protocol, a relative decrease in yield of antigen-specific hybridomas was found in the long term IL-4 treated mice. Immunohistological staining of spleen sections from mice treated with IL-4 up until the time of booster revealed reduced B-cell follicle area and germinal centre numbers. These results show that extensive IL-4 treatment reduced antigen-specific B-cell formation and suggests a reduction in the number of B cells entering the memory B-cell pathway in the spleen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1995.tb03594.x
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  • 2
    Electronic Resource
    Electronic Resource
    Increased intestinal permeability during cytomegalovirus infection in renal transplant recipients (1996)
    Springer
    Transplant international 9 (1996), S. 576-580 
    Details
    ISSN: 1432-2277
    Keywords: CMV, renal transplantation, intestinal permeability kwRenal transplantation, CMV, intestinal permeability ; Permeability, intestinal, CMV ; Intestinal permeability, renal transplantation, CMV
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cytomegalovirus (CMV) infections in renal transplant recipients can affect the gastrointestinal tract, but significant clinical manifestations are seldom seen. We hypothesize that subclinical involvement of the gastrointestinal tract may be quite frequent during CMV infection. In order to study this, we measured intestinal permeability by calculating the urinary lactulose mannitol (LM) excretion ratio after oral administration of lactulose and mannitol (normal〈0.030) in patients with symptomatic and asymptomatic CMV infection. A total of 111 patients were enrolled in the study, 104 of whom were tested on postoperative day (POD) 10. Twenty-nine patients developed CMV infection, 12 of whom could be studied with the permeability test (median POD 40). Another nine patients without CMV infection were also studied at day 40 and served as controls. The LM ratio increased significantly during CMV infection compared to measurements before active infection (median 0.060 vs. 0.030, P〈0.01) and was significantly higher during the infection than in the control group (median 0.007, P〈0.01). No correlation could be found between the LM ratio and viral load, humoral response to the virus, or symptomatology of infection. We conclude that an increased intestinal permeability is found in a substantial number of patients with an active, albeit asymptomatic, CMV infection after renal transplantation. Pathophysiological mechanisms and clinical implications remain speculative but will be subject to further study.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00335558
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  • 3
    Electronic Resource
    Electronic Resource
    Approaches to lung cancer treatment using the CD3E×GP-2-directed Bispecific Monoclonal Antibody BIS-1 (1997)
    Springer
    Cancer immunology immunotherapy 45 (1997), S. 203-206 
    Details
    ISSN: 1432-0851
    Keywords: Key words Lung cancer ; CD3×EGP-2 ; Bispecific monoclonal antibody
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The bispecific monoclonal antibody (bsAb) BIS-1 combines a monoclonal-antibody(mAb)-defined specificity for the CD3 complex, as present on all T lymphocytes, with a mAb-defined specificity for the pancarcinoma/epithelium associated glycoprotein EGP-2. In vitro studies indicate that BIS-1 can direct T lymphocytes to kill EGP-2-positive tumour target cells. T cell pre-activation is necessary for this activity and can be obtained either via incubation of isolated peripheral blood mononuclear cells with CD3 mAb, followed by short culturing in recombinant interleukin-2-containing medium, or via costimulation with CD5- and CD28-based bsAb. Clinical application of BIS-1 was started in a pilot study in which carcinoma patients suffering from malignant ascites or intrapleural effusion were treated. In this study, ex vivo activated autologous lymphocytes were applied locally, i.e. intraperitoneally or intrapleurally, in the presence of BIS-1. Local inflammation and antitumour activity were observed, whereas no or only minor systemic toxicity was seen in these patients. Intravenous administration of BIS-1 F(ab′)2 in combination with subcutaneously given recombinant interleukin-2 (i.v. bsAb/rIL-2 treatment) induced transient but considerable toxicity including peripheral vasoconstriction, dyspnoea and fever with a maximal tolerated dose of 5–8 μg/kg. High plasma concentrations of the inflammatory cytokines tumor necrosis factor α and interferon γ were observed at this dose. Whereas bsAb-dictated antitumour activity could be demonstrated to be present in blood samples of these patients in an in vitro assay, no clear clinical responses were observed. In a rat model it was found that i.v. bsAb/rIL-2 treatment of EGP-2-positive tumours was effective when a low systemic tumour burden was present, suggesting that systemic bsAb/rIL-2 treatment might be effective in situations of minimal residual disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002620050433
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  • 4
    Electronic Resource
    Electronic Resource
    Quantification of immunosuppression by flow cytometric measurement of intracellular cytokine synthesis (1998)
    Springer
    Transplant international 11 (1998), S. S318 
    Details
    ISSN: 1432-2277
    Keywords: Key words Cytokine synthesis ; Flow cytometry ; T cells ; Cyclosporine A ; Whole blood
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The availibility of a method to measure the effects of drugs on immune reactivity should be helpful in optimizing treatment after organ transplantation. Since cyclosporine A (CSA) interferes with activation of T cells and cytokine synthesis, production of IL-2 and IFN-γ might constitute a marker of this drug's effects. We measured the capacity for mitogen-stimulated production of these cytokines in whole blood by using immunostaining of intracellular and membrane antigens, followed by flow cytometry. The percentage of CD4+ T cells producing IL-2 or IFN-γ was strongly reduced in 20 transplant patients compared with 24 healthy controls. The capacity for IL-2 production of CD4+ and CD8+ cells correlated inversely with CSA blood levels (P values 0.0087 and 0.0396, respectively). IFN-γ production by CD4+ T cells showed a negative correlation with the prednisolone dose (P = 0.0175) and, for the CD8+ subset, with CSA trough levels (P = 0.0023). These data show that inhibition of T cell cytokine synthesis by CSA and prednisolone can be quantified.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050487
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  • 5
    Electronic Resource
    Electronic Resource
    Donor-specific immunological non-responsiveness after liver transplantation (1998)
    Springer
    Transplant international 11 (1998), S. S239 
    Details
    ISSN: 1432-2277
    Keywords: Key words Donor-specific immunological non-responsiveness ; Cytotoxic T cells ; Mixed lymphocyte culture ; Liver transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Since the rate of immunological losses of liver allograft after the immediate posttransplant period is much lower than in other organs, we studied the immune responses against donor HLA antigens in 18 patients with a good long-term outcome to determine whether the development of a state of immunological non-responsiveness to donor antigens might account for this favorable outcome. The reactivity against donor spleen cells was measured before and 2 years after transplantation. The reactivity in mixed lymphocyte culture (MLC) and the frequencies of cytotoxic T cell precursors (CTLp) were determined. Responses against third-party spleen cells were determined concurrently to exclude a generalized reduction of immunocompetence due to chronic immunosuppressive treatment. Before orthotopic liver transplantation, the majority of patients had normal T cell responses against donor antigens that were comparable to those against third-party antigens. Two years after transplantation, donor-specific MLC non-reactivity had developed in 10 of the 18 (56 %) patients. In addition, 15 of 18 (83 %) patients had developed donor-specific cytotoxic T cell (CTL) non-responsiveness; 2 had reduced numbers of CTLp against both donor and third-party cells, while the remaining patient had maintained reactivity against donor antigens. In conclusion, donor-specific non-responsiveness is present in the majority of patients 2 years after successful liver transplantation, but occurs predominantly at the CTL level.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050468
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  • 6
    Electronic Resource
    Electronic Resource
    Cytomegalovirus pneumonitis after kidney transplantation is not caused by plugging of cytomegalic endothelial cells only (1999)
    Springer
    Transplant international 12 (1999), S. 56-62 
    Details
    ISSN: 1432-2277
    Keywords: Key words Cytomegalovirus ; kidney transplantation ; Pneumonitis ; kidney transplantation ; Kidney transplantation ; pulmonary diffusion ; Pulmonary diffusion ; cytomegalovirus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In addition to life-threatening pneumonia, cytomegalovirus (CMV) may also cause subclinical pulmonary dysfunction after kidney transplantation. To investigate the role of plugging of cytomegalic endothelial cells in the pulmonary capillary bed, we prospectively determined specific carbon monoxide diffusion capacity (KCOc) and its components: the pulmonary diffusing membrane factor (Dm) and pulmonary capillary blood volume (Vcap) before and during CMV infection in 13 kidney transplant recipients and 13 controls. During CMV infection, mean KCOc decreased significantly by 28 % of the initial value (mean KCOc 79 vs 109; P 〈 0.005 ) due to a decrease in both Vcap and Dm. The KCOc in controls showed a significantly smaller decrease due to a slightly lower Vcap. We conclude that kidney transplant recipients with CMV infection have significant pulmonary diffusion disturbances due to a combination of lower Vcap and lower Dm. The most likely explanation for this phenomenon is a local inflammatory process due to CMV and not plugging of cytomegalic endothelial cells only.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050185
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