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  • 1
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    A defect in the early phase of T-cell receptor-mediated T-cell activation in patients with common variable immunodeficiency (1994)
    American Society of Hematology
    Details
    Publication Date: 1994-12-15
    Description: Common variable immunodeficiency (CVID) is characterized by an impairment of specific antibody production and a decrease in all or selected Ig isotypes. Abnormalities at the level of the B cells, T cells, and antigen-presenting cells have been described. In the present study, we have focused our attention on T-cell activation in CVID. T cells from 15 of 24 patients failed to respond to recall antigens (eg, tetanus toxoid, Escherichia coli). Of these 15 patients, 11 were studied in detail and showed significantly decreased T-cell proliferative responses and/or decreased interleukin-2 and interferon- gamma production on T-cell receptor-mediated stimulation with recall antigens and superantigens (staphylococcal enterotoxins [SE]); however, T-cell response to mitogens (anti-CD3 monoclonal antibody, phytohemagglutinin) was normal. The defect in interleukin-2 and interferon-gamma release on tetanus toxoid stimulation could also be documented in purified CD4 T cells of the patients and was present in patients with high and normal CD8 counts alike. Furthermore, patients' T cells failed to mount a significant elevation in free intracellular calcium (Ca++ flux) in response to superantigen, whereas the response to phorbol myristate acetate and ionomycin, bypassing receptor-mediated signaling, was unimpaired. These results indicate a defect in the early phase of T-cell activation after triggering of the T-cell receptor in a significant subgroup of CVID patients.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 2
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    Human serum IgA downregulates the release of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6) in human monocytes (1994)
    American Society of Hematology
    Details
    Publication Date: 1994-03-01
    Description: While the protective effect of IgA antibodies against infection of the mucosal surfaces is well documented, the mechanisms involved are not entirely clear. The aim of the current study is to investigate the effect of human serum IgA on the release of inflammatory cytokines in human monocytes activated with a particulate stimulus, Haemophilus influenzae type b (Hib), or soluble lipopolysaccharide (LPS) purified from Escherichia coli. Our results show that IgA downregulates tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) production, whereas IgG examined in parallel had no effect. IgA had no inhibitory effect on Hib-induced granulocyte-macrophage colony-stimulating factor release. TNF-alpha and IL-6 release were downmodulated if IgA was present during cytokine induction, and IgA was also inhibitory if added to Hib-pretreated monocytes during the phase of cytokine release. These findings indicate that there are at least two mechanisms whereby IgA antibodies can downregulate TNF-alpha and IL-6 release in human monocytes: by a mechanism acting during the time of monocyte activation, and a mechanism that downregulates the production and/or the release of these cytokines in activated monocytes. Regulation of TNF-alpha and IL-6 release by IgA may be among the antiinflammatory mechanisms preventing an uncontrolled release of potentially noxious levels of inflammatory cytokines during acute and/or chronic inflammation.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 3
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    A component of factor VIII preparations which can be separated from factor VIII activity down modulates human monocyte functions (1987)
    American Society of Hematology
    Details
    Publication Date: 1987-04-01
    Description: In this study we investigated different aspects of monocyte functions following interaction of monocytes (Mo) with therapeutic concentrations of factor VIII (F VIII) concentrate. A short (one-hour) treatment of normal Mo with F VIII concentrates led to a significant (P less than 0.001) down modulation of Fc receptors expressed in the Mo plasma membrane. This down modulation was accompanied by a decrease of Mo effector functions that was expressed by a reduced capacity of F VIII- treated Mo to release O2 radicals (40% of controls) and to kill bacteria (% killing: control Mo, 65%; F VIII-treated Mo, 24% to 51%). Further studies showed that the modulating activity was due to a contaminant present in F VIII concentrates (immune complexes or IgG aggregates). Fractionation using molecular sieving revealed that the modulatory activity was confined to a high-molecular range fraction (Mr greater than 1,270,000 daltons), while the fraction containing monomeric IgG had no effect. Further fractionation by affinity chromatography on protein A-Sepharose separated the coagulation activity (effluent) from the Mo function-modulating activity (eluate). We conclude that treatment with F VIII concentrates might contribute to an immunocompromised state in some hemophiliacs and facilitate opportunistic infections in these patients.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 4
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    Comparable modulation of human monocyte functions by commercial factor VIII concentrates of varying purity (1988)
    American Society of Hematology
    Details
    Publication Date: 1988-06-01
    Description: Our previous observation on immune modulation induced by a given factor VIII (F VIII) concentrate preparation was extended by showing that the immune-modulating capacity is a more general feature of F VIII products and is independent of product purity. Interaction of human monocytes with therapeutic concentrations of various F VIII concentrates (0.2 to 2 IU F VIII/mL, six different F VIII concentrates from four manufacturers) led to a significant reduction in the expression of IgG Fc receptors in the membrane of these cells (F VIII concentrate-induced downmodulation of the receptor). This Fc receptor downmodulation was achieved by a short (1-hour) incubation of human monocytes with F VIII concentrates 16 hours prior to the Fc receptor assay and did not correlate with the respective product's IgG content. Although the IgG concentrations of the different products varied greatly (from 1.0 to 177.3 mg/1,000 IU F VIII), all products behaved comparably with respect to Fc receptor downmodulation (F VIII-treated monocytes: 34% +/- 7% to 44% +/- 4% rosette-forming cells; controls in the absence of F VIII: 83% +/- 5%). Furthermore, we also were able to demonstrate that heat treatment of F VIII, now used by virtually every manufacturer to eliminate contaminating viruses, had no effect on the respective products' Fc receptor-modulating capacity. The immune-modulating component was characterized as being a high-molecular-range compound containing IgG, IgM, F VIII, and blood group substances (most likely a combination of immune complexes and immunoglobulin aggregates). This compound is present in comparable amounts in both high-purity and intermediate-purity products and apparently copurifies with F VIII during the manufacturing process.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 5
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    Unknown
    A component of factor VIII preparations which can be separated from factor VIII activity down modulates human monocyte functions (1987)
    American Society of Hematology
    Details
    Publication Date: 1987-04-01
    Description: In this study we investigated different aspects of monocyte functions following interaction of monocytes (Mo) with therapeutic concentrations of factor VIII (F VIII) concentrate. A short (one-hour) treatment of normal Mo with F VIII concentrates led to a significant (P less than 0.001) down modulation of Fc receptors expressed in the Mo plasma membrane. This down modulation was accompanied by a decrease of Mo effector functions that was expressed by a reduced capacity of F VIII- treated Mo to release O2 radicals (40% of controls) and to kill bacteria (% killing: control Mo, 65%; F VIII-treated Mo, 24% to 51%). Further studies showed that the modulating activity was due to a contaminant present in F VIII concentrates (immune complexes or IgG aggregates). Fractionation using molecular sieving revealed that the modulatory activity was confined to a high-molecular range fraction (Mr greater than 1,270,000 daltons), while the fraction containing monomeric IgG had no effect. Further fractionation by affinity chromatography on protein A-Sepharose separated the coagulation activity (effluent) from the Mo function-modulating activity (eluate). We conclude that treatment with F VIII concentrates might contribute to an immunocompromised state in some hemophiliacs and facilitate opportunistic infections in these patients.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 6
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    Unknown
    Human serum IgA downregulates the release of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6) in human monocytes (1994)
    American Society of Hematology
    Details
    Publication Date: 1994-03-01
    Description: While the protective effect of IgA antibodies against infection of the mucosal surfaces is well documented, the mechanisms involved are not entirely clear. The aim of the current study is to investigate the effect of human serum IgA on the release of inflammatory cytokines in human monocytes activated with a particulate stimulus, Haemophilus influenzae type b (Hib), or soluble lipopolysaccharide (LPS) purified from Escherichia coli. Our results show that IgA downregulates tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) production, whereas IgG examined in parallel had no effect. IgA had no inhibitory effect on Hib-induced granulocyte-macrophage colony-stimulating factor release. TNF-alpha and IL-6 release were downmodulated if IgA was present during cytokine induction, and IgA was also inhibitory if added to Hib-pretreated monocytes during the phase of cytokine release. These findings indicate that there are at least two mechanisms whereby IgA antibodies can downregulate TNF-alpha and IL-6 release in human monocytes: by a mechanism acting during the time of monocyte activation, and a mechanism that downregulates the production and/or the release of these cytokines in activated monocytes. Regulation of TNF-alpha and IL-6 release by IgA may be among the antiinflammatory mechanisms preventing an uncontrolled release of potentially noxious levels of inflammatory cytokines during acute and/or chronic inflammation.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
    Location Call Number Expected Availability
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  • 7
    facet.materialart.
    Unknown
    Comparable modulation of human monocyte functions by commercial factor VIII concentrates of varying purity (1988)
    American Society of Hematology
    Details
    Publication Date: 1988-06-01
    Description: Our previous observation on immune modulation induced by a given factor VIII (F VIII) concentrate preparation was extended by showing that the immune-modulating capacity is a more general feature of F VIII products and is independent of product purity. Interaction of human monocytes with therapeutic concentrations of various F VIII concentrates (0.2 to 2 IU F VIII/mL, six different F VIII concentrates from four manufacturers) led to a significant reduction in the expression of IgG Fc receptors in the membrane of these cells (F VIII concentrate-induced downmodulation of the receptor). This Fc receptor downmodulation was achieved by a short (1-hour) incubation of human monocytes with F VIII concentrates 16 hours prior to the Fc receptor assay and did not correlate with the respective product's IgG content. Although the IgG concentrations of the different products varied greatly (from 1.0 to 177.3 mg/1,000 IU F VIII), all products behaved comparably with respect to Fc receptor downmodulation (F VIII-treated monocytes: 34% +/- 7% to 44% +/- 4% rosette-forming cells; controls in the absence of F VIII: 83% +/- 5%). Furthermore, we also were able to demonstrate that heat treatment of F VIII, now used by virtually every manufacturer to eliminate contaminating viruses, had no effect on the respective products' Fc receptor-modulating capacity. The immune-modulating component was characterized as being a high-molecular-range compound containing IgG, IgM, F VIII, and blood group substances (most likely a combination of immune complexes and immunoglobulin aggregates). This compound is present in comparable amounts in both high-purity and intermediate-purity products and apparently copurifies with F VIII during the manufacturing process.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
    Location Call Number Expected Availability
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    PAPER CURRENT
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