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Biomedical subjects

G C Mudde

Publications and source records attributed to G C Mudde.

51 records · Page 3Linked to original sources
PubMed1989

Role of Langerhans cells in atopic disease.

So far, the role of antigen-presenting cells in atopic disorders has been underestimated. Recent observations, made in the skin of patients with atopic dermatitis and in the nasal mucosa of patients with allergic rhinitis suggest that Langerhans cells, being tissue-specific dendritic cells with potent antigen-presenting capacity, play an important role in the allergic inflammatory response. Evidence is presented that Langerhans cells even play a crucial role in directing the type of the allergic reaction mechanism.

Dermatitis, Atopic↗
PubMed1989

The presence of IgE molecules on epidermal Langerhans cells in atopic dermatitis and their significance for its pathogenesis.

Aeroallergens can induce a delayed patch test reaction, which is specific for patients with atopic dermatitis (AD). Histopathology of this aeroallergen induced skin reaction suggests the involvement of Langerhans cells (LC), T cells and eosinophils. Since LC from AD patients may bear Fc sigma, R-bound IgE molecules, it was hypothesized that aeroallergens after contact with the skin bind to allergen-specific IgE on LC leading to efficient presentation to T cells. In vitro studies show that LC from AD patients can indeed present aeroallergens to T cells, provided LC-bound IgE molecules are present. These results, firstly, explain the reaction mechanism behind the patch test reaction to aeroallergens; secondly, they point to a new allergic reaction mechanism in which a link is provided between type I and type IV allergic reactions according to Gell and Coombs; thirdly, they throw a new light on the role of aeroallergens in the pathogenesis of AD. Aeroallergens may after contact with skin of AD patients not only induce eczematous skin lesions but also be involved in the induction of the synthesis of allergen specific IgE molecules. From a practical point of view, the results of this study show that aeroallergens play a more important role in the pathogenesis of AD than has been accepted so far.

Dermatitis, Atopic↗
PubMed1989

The spot-ELISA: a sensitive in vitro method to study the immune response to hepatitis B surface antigen.

We present our experience with a new sensitive in vitro method for the study of the immune response to hepatitis B surface antigen (HBsAg). This immunoenzymatic technique, called spot-ELISA, detects specific immunoglobulin production (e.g. IgG- or IgM-anti-HBs) by stimulated individual B cells in vitro. We have studied the immune response against HBsAg by mitogenic stimulation and subsequent spot-ELISA assay in 24 well-documented subjects with known immune status after either natural infection or vaccination with plasma-derived vaccine. Results indicate a good correlation between in vitro IgG anti-HBs spots and immune 'memory.' A possible predictive value in non-immunized and non-responder subjects awaits further confirmation.

Cells, Cultured↗
PubMed1988

Associated expression of CD1 antigen and Fc receptor for IgE on epidermal Langerhans cells from patients with atopic dermatitis.

The presence of Fc receptors for IgE on epidermal Langerhans cells (LC) from patients with atopic dermatitis (AD) was demonstrated by three different types of experiments. Firstly, cell-bound IgE on LC was removed by acid elution and restored by highly purified human myeloma IgE (IgE kappa). Secondly, after pepsin digestion of cell-bound IgE the number of LC staining with anti-human light chain (kappa, lambda) antibodies significantly decreased in contrast to the number of LC staining with anti-human epsilon heavy chain antibody. Thirdly, LC formed rosettes with sheep red blood cells (SRBC) coated with IgE kappa. Epidermal LC from normal non-atopic controls, did not form rosettes with SRBC-IgE. The SRBC-IgE rosette formation could be inhibited by preincubation with IgE kappa and BB10 (MoAb directed against the Fc receptor for IgE on human eosinophils, platelets and macrophages), but also with human IgG, whereas the SRBC-IgG rosette formation could be inhibited neither by IgE kappa nor by BB10. Both the SRBC-IgE and the SRBC-IgG rosette formation could be inhibited by OKT6 (anti-CD1) antibody. The results of inhibition studies with OKT6 antibody on the reconstitution of IgE on epidermal LC after acid elution suggest an associated expression of the CD1 antigen and the Fc receptor for IgE.

Antigens, Differentiation↗
PubMed1987

Cytomegalovirus seronegative platelets and leukocyte-poor red blood cells from random donors can prevent primary cytomegalovirus infection after bone marrow transplantation.

The effect of a deliberate transfusion policy for prevention of primary cytomegalovirus (CMV) infection, consisting of leukocyte-poor red blood cells from random donors and platelets from CMV-negative donors, was studied in 29 CMV-negative negative recipients of an allogeneic (from CMV-negative donors) or autologous bone marrow transplant. All transplant recipients remained CMV-negative with this approach. Such a policy depends on the availability of CMV-negative platelet donors. Siblings from CMV-negative marrow transplantation candidates appeared to be more often CMV-negative than siblings from CMV-positive transplantation candidates (77% versus 34%, p less than 0.001). Selection of CMV-negative blood bank donors for transfusion of blood products is also easy to perform. As a consequence, CMV-negative marrow transplant recipients have a good chance of receiving CMV-negative marrow transplants and blood products and primary CMV infection can thus be prevented by this transfusion policy.

Anemia, Aplastic↗
PubMed1986

Induction of IgM production by pokeweed mitogen and interleukin-2: different responses by human peripheral blood cells and tonsil cells.

Stimulation of tonsils or peripheral blood lymphocytes with either pokeweed mitogen (PWM) or interleukin-2 (IL-2) results in significant IgM production. However, the combination of PWM and IL-2 shows a synergistic IgM synthesis in tonsil cells, whereas the secretion in peripheral blood cells is diminished compared to activation with either stimulus alone. The heavy-chain isotype distribution does not significantly change in the two cell types when stimulated with either PWM, IL-2, or the combination. The Ig synthesis by tonsil cells to PWM or IL-2 drastically increases in the presence of monocytes, but the response to PWM + IL-2 together is not affected. The reason for the synergistic IgM production to PWM + IL-2 in tonsil cells is the relative lack of monocytes and the low number of T8+-suppressor cells. The decreased IgM production in peripheral blood cells after stimulation with both PWM and IL-2 is due to the presence of T8+ cells. These data show that the monocyte-dependent IL-2 production is an essential step in PWM-induced Ig secretion; the subsequent induction of the T-cell-helper signal for B-cell differentiation is determined by the balance between the strength of the stimulus for T cells and the T4/T8 ratio. Hence, these parameters should be included when the B-cell function is studied in vitro with the use of PWM and IL-2.

Antigen-Presenting Cells↗
PubMed1986

Human peripheral blood B cell subpopulations: surface IgD+ cells respond to pokeweed mitogen with plasma cell differentiation.

Human peripheral blood (PB) mononuclear cells were depleted of T cells and subsequently of monocytes by counterflow centrifugation. The resulting B cell enriched fraction contained less than 3% T cells, 1 +/- 1% monocytes and 71 +/- 6% B cells. Approximately 56% of the B cells carried surface IgM (sIgM) and sIgD, the remaining 44% carried only one isotype (IgG, IgA, IgM or IgD). Using anti-delta or anti-mu-coated Ox red blood cells (OxRBC) the B cell enriched fraction was separated into a sIgD+ or sIgM+ and sIgD- or sIgM- fraction. The sIgD+ as well as the sIgM+ fraction responded (partially) to pokeweed mitogen (PWM) with plasma cell differentiation into cytoplasmic IgM (cIgM) containing cells. Cytoplasmic IgD+ cells were occasionally found in the sIgD+ or sIgM- fraction, but never in the sIgM+ fraction. Cells containing cIgG or cIgA were only found after stimulation of the sIgM- or sIgD- fraction, the latter also produced cIgM+ cells. In a second separation step of the sIgD- and sIgM- fraction with anti-alpha or anti-gamma-coated OxRBC it was shown that the cIgA+ and cIgG+ cells were derived from B cells expressing only sIgA or sIgG respectively. In conclusion, two major B cell subpopulations can be found in PB: a sIgM+D+ fraction, which gives rise to only cIgM+ plasma cells after PWM stimulation and a second population of B cells which express one heavy-chain isotype on their surface. These cells not only differentiate on PWM stimulation, but they also show a strong proliferative response.

Adult↗
PubMed1984

Human tonsil B lymphocyte function. II. Pokeweed mitogen-induced plasma cell differentiation of B cell subpopulations expressing multiple heavy chain isotypes on their surface.

Human tonsil non-T cells were successfully separated into surface IgM+G-ve (sIgM+G-), sIgM+G+, sIgM-G-, and sIgM-G+ B cell fractions. The two-step separation technique used did not affect the pokeweed mitogen- (PWM) induced plasma cell differentiation of the B cells. The highest percentages of plasma cells after PWM stimulation were found in the sIgM- fractions, and the lowest percentage was in the sIgM+G- fraction (20.8 +/- 2.3%), the latter predominantly cytoplasmic mu-chain-positive (c mu +) (84.1 +/- 3.5%) plasma cells. In this fraction, almost no c gamma + plasma cells were found. The sIgM+G+ produced c mu + (47.5 +/- 7.5%), c gamma + (35.7 +/- 5.8%), and c alpha + (16.8 +/- 4.0%) plasma cells. All three isotypes were found on the surface of the B cells in this fraction before PWM stimulation. The sIgM-G- fraction contained about 10% plasma cells before stimulation, which were predominantly c gamma +. After PWM stimulation, primarily c alpha + (64.2 +/- 4.3%) plasma cells were found. The sIgM-G+ fraction produced both c gamma + (75.0 +/- 2.3%) and c alpha + (24.1 +/- 2.5) plasma cells. A mu to gamma class switch did not occur in vitro in the sIgM+G- fraction on PWM stimulation, and the sIgM+G+ fraction did not complete in vitro the mu to gamma switch it had started in vivo.

B-Lymphocytes↗
PubMed1984

Human tonsil B lymphocyte function. I. The proliferative response to Staphylococcus aureus and pokeweed mitogen in relation to surface heavy chains mu and delta.

Human tonsil non-T cells were separated into surface IgD positive (sIgD+), surface IgD negative (sIgD-), sIgM+ and sIgM- fractions by rosetting and gradient centrifugation with ox red blood cells, coated with immunosorbent purified goat anti-human heavy chain antibodies. No activation or suppression was found as a result of the separation technique. The sIg patterns of the isolated B cell fractions showed the effectiveness of the separations; sIgD+ and sIgM+ fractions were to a great extent overlapping populations, but there was a definite population of s mu + delta- cells (about 20% of the sIgD- fraction). The isolated fractions were tested for proliferative responses to Staphylococcus aureus (Sta) and pokeweed mitogen (PWM). The sIgM+ fraction showed the best response to Sta, eight times better than the sIgM- fraction, while the sIgD+ and sIgD- fraction showed equal responses to Sta. The sIgM- fraction responded best to PWM but all fractions responded quite well. Our results indicate that PWM is a mitogen to a whole variety of rather mature B cells while the Sta target B cell is restricted to the relatively immature sIgM+D- and sIgM+D+ cells.

B-Lymphocytes↗
PubMedDate not supplied

Prevention of primary cytomegalovirus infection in patients with hematologic malignancies by intensive white cell depletion of blood products.

The effect of white cell depletion of red cells and platelet concentrates on the transmission of cytomegalovirus (CMV) was studied retrospectively in 150 patients treated intensively for acute leukemia or non-Hodgkin's lymphoma. CMV infection was diagnosed on the basis of IgM and IgG antibody responses to CMV late antigen (CMV-LA). Before cytoreductive therapy for their underlying disease, 59 patients were CMV seronegative and 91 were CMV seropositive. None of the 59 CMV-seronegative patients showed persistent seroconversion 2 months after the cytoreductive treatment. The comparison group, consisting of 312 cardiac surgery patients, showed a significantly higher incidence of primary CMV infections: 10 of 86 (11.6%, p = 0.004). Twenty-five percent of the CMV-seronegative patients and controls had transient IgG antibodies to CMV-LA without IgM antibodies, which is indicative of antibodies passively acquired via blood products. These results indicate that white cell-poor blood products carry a very low risk, if any, of CMV transmission. The policy of transfusing white cell-poor blood products provides a useful alternative to the selection of CMV-seronegative donors.

Adult↗