Biomedical subjects

F L van der Heijden

Publications and source records attributed to F L van der Heijden.

9 recordsLinked to original sources

PubMed1995

Relationship between facilitated allergen presentation and the presence of allergen-specific IgE in serum of atopic patients.

Allergen presentation to allergen-specific T cells can be facilitated when IgE-allergen complexes are endocytosed by antigen-presenting cells (APC) after binding to the low-affinity Fc epsilon R type II (CD23). Here we present a study on the relative capabilities of sera of atopic patients to mediate facilitated antigen presentation (FAP). To this aim FAP was studied in an in vitro model in which CD23-expressing Epstein-Barr virus (EBV)-B cells act as APC to T lymphocyte clones (TLC) that are specific for Der p 2, a major allergen of housedust mite Dermatophagoides pteronyssinus (Dp). Der p 2 is immune-complexed by preincubation in sera from atopic patients, containing allergen-specific IgE. If EBV-B cells are preincubated with these complexes before using the cells as APC, the allergen-specific TLC proliferate at 100-1000-fold lower allergen concentration than required for T cell activation after presentation of uncomplexed allergen. The relative capability of various sera to mediate FAP was correlated with total serum IgE, and especially with Der p 2-specific serum IgE. In the model used, a high FAP capacity could be demonstrated only in sera with a total serum IgE concentration above approximately 2 micrograms/ml or with Der p 2-specific IgE above approximately 100 ng/ml. Maximal FAP, i.e. the ability to induce maximal proliferation of the TLC, was obtained in the presence of more than +/- 600 ng Der p 2-specific IgE/ml. At 100-600 ng/ml Der p 2-specific IgE the level of FAP was correlated with the concentration of allergen-specific IgE, whereas at lower concentrations FAP was low or absent. All tested sera from eczema patients, all having serum anti-Der p 2-IgE concentrations > 600 ng/ml, showed a high FAP capacity, whereas all tested sera from atopic patients without eczema, which had serum anti-Der p 2-IgE levels < 600 ng/ml, showed no or a low FAP capacity. The association of high FAP capacity with eczema may reflect a functional role of FAP in the pathogenesis of atopic dermatitis.

Allergens↗

PubMed1994

Characterization of lesional psoriatic skin T lymphocyte clones.

T cells are considered to play a role in the pathomechanism of psoriasis. Therefore we investigated the cytokine production patterns of T cell clones that were randomly prepared from chronic plaque psoriasis lesions of 2 patients. 67% of the 49 T lymphocyte clones (TLC) expressed CD4 and 33% expressed CD8 (ratio 2:1), while gamma delta-TCR expression was absent. The production of IL-4, IFN-gamma, IL-2 and IL-6 was measured in supernatants of TLC following PHA plus PMA stimulation. Different groups of clones could be distinguished according to their IL-4/IFN-gamma production ratio. In addition to Th0 cells (low IL-4/low IFN-gamma), low IL-4/high IFN-gamma producers as well as high IL-4/low IFN-gamma producing clones were found, suggesting the presence of Th1- and Th2-like subsets. Upon stimulation, all TLC secreted low levels of IL-2 whereas a minority of the TLC secreted low levels of IL-6. These results may imply that T cells in psoriasis lesions do not show shifts towards either a Th1 or a Th2 cytokine production profile.

CD4-CD8 Ratio↗

PubMed1993

Serum-IgE-facilitated allergen presentation in atopic disease.

The occurrence of facilitated Ag presentation (FAP) was investigated in atopic disease using an in vitro model in which the ability of CD23-expressing EBV-B cells was tested to present Der p II, a major allergen of housedust mite Dermatophagoides pteronyssinus, to cells of autologous Der p II-specific CD4+ T lymphocyte clones. Purified Der p II protein was immune complexed with Ig by preincubation in sera from atopic patients containing Der p II-specific IgE. Incubation of EBV-B cells with these complexes before using the cells as APC results in proliferation of the Der p II-specific T cells at a 1000-fold lower Der p II concentration than required for T cell activation by presentation of uncomplexed Der p II. FAP is not evident using sera from allergic and nonallergic control donors not containing Der p II-specific IgE. FAP is mediated by IgE and not by IgG, because it can be blocked completely by preincubating the serum from atopics with polyclonal anti-IgE and not with polyclonal anti-IgG. After pulsing EBV-B with precomplexed Der p II at 4 degrees C, FAP is as strong as after incubation at 37 degrees C, suggesting that FAP is the result of facilitated trapping of IgE-complexed allergen. CD23 was involved in facilitated trapping of the complexes, because FAP is blocked by preincubation of EBV-B with anti-CD23. In contrast to FAP of Der p II, which was mediated by all Der p II-specific sera tested, only one of four sera containing cat allergen-specific IgE was appropriate to mediate FAP to cat allergen-specific T cell clones. Inasmuch as FAP enables functional presentation of allergen in vivo at doses as low as several nanograms, FAP may contribute to the continuing of chronic allergic reactions in response to minute doses of aeroallergens, especially housedust mite allergens, in the environment.

Allergens↗

PubMed1992

Immune dysregulation in atopic eczema.

BACKGROUND: In this review, present knowledge of atopic eczema immunopathogenesis is summarized, emphasizing recent new findings. Systemic abnormalities in cell-mediated immunity have not been demonstrated firmly in patients with atopic eczema. Within the skin itself, there is evidence for decreased cell-mediated immunity, which is partially correlated with the severity of skin disease. Atopic eczema, however, cannot be regarded as a direct result of decreased cutaneous cell-mediated immunity, since immunophenotyping studies have revealed activated T cells as well as dendritic cells within involved skin. In addition, disease marker studies in peripheral blood indicate vigorous T-cell activation in atopic dermatitis. OBSERVATIONS: The original observation of IgE molecules on the membranes of Langerhans cells may indicate trapping of IgE allergen complexes, their processing, and subsequent presentation to allergen-specific T cells within involved skin. Recent findings as to the abnormal regulation of IgE synthesis in atopy point to a preferential expansion of interleukin 4 and interleukin 5 producing allergen-specific T cells, leading to increased production of interleukin 4 and thus increased levels of allergen-specific IgE. We have prepared atopic skin as well as peripheral blood-derived T-cell clones and determined their specificity and cytokine production profile. Results indicate in situ production of interleukin 4 and interleukin 5 within involved skin in response to environmental antigens. CONCLUSIONS: These new findings as to the basis of IgE dysregulation in atopy, as well as to the identification of an abnormal cytokine secretion pattern by T cells presumed to be central in immunopathogenesis of atopy-related disorders, suggest a distorted and cytokine-mediated self-perpetuating response of the skin immune system to environmental allergen(s) in the pathogenesis of skin disease in atopy. These observations may have important implications for the development of new therapies for atopic eczema.

Dermatitis, Atopic↗

PubMed1991

High frequency of IL-4-producing CD4+ allergen-specific T lymphocytes in atopic dermatitis lesional skin.

In atopic dermatitis (AD) hypersensitivity reactions to allergens are commonly observed and are assumed to make a major contribution in the pathomechanism of the disease. It may be expected that allergen-reactive Th cells play a central role in these reactions. In the present study the occurrence and function of allergen-specific T lymphocytes in dermal inflammatory lesions were studied. To this aim panels of randomly cloned CD4+ T cells from lesional skin biopsies of two housedust mite Dermatophagoides pteronyssinus (Dp)-allergic AD patients were screened for reactivity with Dp allergens. The results were compared with similar tests for Dp reactivity of T-lymphocyte clones (TLC) from the peripheral blood of these patients. In the panels of TLC generated from lesional skin (S-TLC), a considerable number of TLC appeared to be Dp-specific, 47% (n = 17) and 10% (n = 29), respectively. In the panels from the peripheral blood, the percentages of Dp-specific TLC were only 0% (n = 22) and 3% (n = 34), suggesting accumulation or expansion of these T cells in lesional skin. The function of these TLC was studied by assaying the secretion of IL-4 and IFN-gamma, which have been shown to be produced in aberrant ratios by Dp-specific TLC from the peripheral blood of AD patients (Wierenga et al: J Immunol 144:4651, 1990). All Dp-specific S-TLC produced IL-4 in combination with no or low levels of IFN-gamma, whereas many of the non-Dp-specific S-TLC and blood-derived TLC (B-TLC) were observed to produce high levels of IFN-gamma without significant amounts of IL-4. A functional consequence of these cytokine profiles was demonstrated by the finding that TLC producing substantial amounts of IL-4 enhanced expression of the low-affinity Fc receptor for IgE (CD23) on antigen-presenting cells to a greater extent than did IFN-gamma-producing TLC.

Adult↗

PubMed1986

Mucosal lymphocytes in the rat small intestine: phenotypical characterization in situ.

Lymphocyte subpopulations in the intestinal mucosa of the rat were quantified in situ and compared with data obtained by other authors using enzymic or mechanical methods (Selby et al., 1984; Gibson et al., 1985) in order to assess any selective loss of cell types or contamination with lamina propria lymphocytes after these enzymic or mechanical isolation procedures. Intraepithelial lymphocytes (IEL) were predominantly of the suppressor/cytotoxic phenotype (MRC OX-8) and nearly all cells bore the pan T marker W3/13. About 10% of the IEL phenotypically belonged to the T-helper (W3/25) lineage. MRC OX-19, the rat equivalent of the mouse Lyt-1 antigen, was present on about 15% of the IEL. The main subpopulation of lamina propria T lymphocytes (T-LPL) showed a T-helper phenotype and a smaller subpopulation a suppressor/cytotoxic phenotype. Practically all T-LPL expressed the pan T marker W3/13, and half of these T cells were MRC OX-19+. The results proved to be in agreement with the data obtained after enzymic or mechanical isolation procedures and indicate that proportional contamination with LPL is not likely to occur with these methods.

Animals↗

PubMed1981

Compensation mechanisms for experimental reduction of the functional capacity in the guinea pig placenta. I. Changes in the maternal and fetal placenta vascularization.

After experimental reduction of its functional capacity, the placenta of the guinea pig has been studied microscopically for changes in the maternal and fetal vascularization pattern which could be interpreted as a compensation for this reduction. The functional capacity has been reduced in four ways. In the experimental groups the volume compared with untreated controls. The volume density of fetal capillaries in the labyrinthine part of the placenta was increased significantly compared with untreated controls. The surface density of these vessels, however, remained the same as in the control placentas. The volume density and surface density of the maternal lacunae did not change significantly. The conclusion is that after experimental reduction of its functional capacity the only structural modification in the guinea pig placenta involving the maternal and fetal vascularization, which can be interpreted as a compensation mechanism, is a widening of the fetal capillaries in the labyrinth.

Animals↗

PubMed1981

Compensation mechanisms for experimental reduction of the functional capacity in the guinea pig placenta. II. Changes in the trophoblast of the labyrinth.

The functional capacity of the placenta of the guinea pig has been reduced in four different ways. It has been investigated whether changes in the trophoblast of the labyrinthine part of the placenta occurred which could be interpreted as a compensation mechanism for the reduction of the capacity. No significant decrease of the thickness of the maternofetal barrier could be measured nor did enlargement by microvilli of the apical and basal surface of the syncytium change significantly. Activities of the enzymes glucose-6-phosphate dehydrogenase, lactate dehydrogenase, glucose-6-phosphatase and adenosine triphosphatase showed a great variation, but no differences in activities could be demonstrated. Further, the number of cytotrophoblastic cells was widely spread and no significant difference could be observed, although sometimes large and apparently newly formed parts of lobulus were observed.

Animals↗

PubMed1975

Polyploidy in the human myometrium.

In an investigation to determine whether the enlargement of cells and nuclei in the myometrium of the human uterus during pregnancy is related to the development of polyploidy or not, the following facts were established, mainly on the basis of cytophotometric analysis of nuclei isolated with a newly developed mechanical technique from a series of uteri in different states with regard to the reproductive process (juvenile, nulligravida, gravida, sectio parva, sectio caesarea). 1. Polyploid nuclei arise only during pregnancy. They can still be found for many years after the puerperium; their occurrence, however, remains a discrete phenomenon. 2. During pregnancy, a swelling of virtually all diploid nuclei is observed, which is present as early as 16 weeks after conception, but a significant increase of the nuclear projection area is found only in the Caesarean section group. This swelling, which (might occur under hormonal influence is possibly of a functional nature and is separate from the development of polyploidy as such. 3. By means of the tracing of double sex chromatin bodies in the nuclei, the occurrence of tetraploid nuclei in the myometrium could be demonstrated both in nuclear suspensions and in sections of intact uterine wall.

Cell Nucleus↗