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Biomedical subjects

J D Bos

Publications and source records attributed to J D Bos.

At least 163 records · Page 9Linked to original sources

Comparison of diversity and function of house dust mite-specific T lymphocyte clones from atopic and non-atopic donors.

Panels of CD4+CD8- T lymphocyte clones (TLC), specific for house dust mite Dermatophagoides pteronyssinus (Dp) proteins, were generated from the peripheral blood of an atopic Dp-allergic donor (AD), suffering from severe atopic dermatitis, and a histocompatible non-atopic donor (NAD). We studied the diversity of TLC within these two panels in search for the possible occurrence of dominant clone types with properties that might be characteristic for the atopic or non-atopic state. TLC with specificities for at least four different Dp proteins were found within the panel from AD "L" and for at least three different Dp proteins within the panel from NAD "K". In addition, both panels showed a considerable but comparable restriction diversity within HLA-DR. Despite the diversity within the panels, all Dp-specific TLC from AD were found to produce IL 4, after HLA class II-restricted Dp-specific stimulation, whereas the TLC from NAD produced no or only minimal amounts of this lymphokine. Only supernatants from stimulated AD TLC could induce IgE secretion by B cells from NAD. Conclusively, these observations do not give evidence for the occurrence of an abnormal Dp-specific T cell repertoire in AD, but rather suggest aberrant secretion of the IgE-inducing lymphokine IL 4 by CD4+ Dp-specific T cells from AD.

Allergens↗

T-cell receptor gamma delta bearing cells in normal human skin.

T-cell antigen receptors (TCR) are divided into common alpha beta and less common gamma delta types. In the murine skin, TCR gamma delta+ cells have been reported to form the great majority of epidermal T lymphocytes. We have examined the relative contribution of TCR alpha beta+ and TCR gamma delta+ cells to the T-cell population in normal human skin. Serial sections of freshly frozen skin specimens were acetone fixed, incubated with anti-CD3, beta F1 (anti-TCR alpha beta), anti-TCR gamma delta-1 and anti-TCR delta 1 (anti-TCR gamma delta) monoclonal antibodies (MoAb), and stained with a highly sensitive method. Over 90% of the T cells of normal human skin are localized around the postcapillary venules of the dermis, while less than 5% are present within the epidermis. In papillary dermis, TCR gamma delta+ cells formed on average 7% (anti-TCR gamma delta-1) or 9% (anti-TCR delta 1) of the total number of CD3+ cells, while TCR alpha beta+ cells constituted up to 80%. In epidermis, these percentages were 18% and 29% for TCR gamma delta+ cells, and up to 60% for TCR alpha beta+ cells. It is concluded that there is no preferential immigration or in situ expansion of TCR gamma delta+ T cells in normal human skin, because the relative percentages found for the TCR alpha beta+ and TCR gamma delta+ populations in skin are comparable to those found in lymphoid organs and peripheral blood. However, the percentage of TCR gamma delta+ cells in epidermis seemed on average higher than in papillary dermis. Therefore, there may still be a difference in migration patterns of TCR gamma delta+ v TCR alpha beta+ cells, but this does not result in their preferential localization in human epidermis. The hypothesis that TCR gamma delta+ T cells have a specialized function in immunosurveillance of epithelia may thus not be valid for human epidermis.

Antigens, CD↗

Human epidermal Langerhans cells undergo profound morphologic and phenotypical changes during in vitro culture.

Morphology, phenotype, and enzyme activity of highly enriched (80%) unlabeled human epidermal Langerhans cells (LC) have been studied, with emphasis on changes during a short-term culture of three days in vitro. All freshly isolated LC contained Birbeck granules and expressed high levels of CD1a, CD1c, and MHC class II molecules HLA-DR, -DP, and -DQ. They have a weak to moderate expression of RFD1, C3biR, Fc gamma R, p 150/95, MHC class I molecules HLA-ABC, and of the adhesion molecules LFA-3 and ICAM-1, whereas no expression of LFA-1 and several monocyte/macrophage markers were detected. Human LC undergo profound changes during in vitro culture. Birbeck granules, C3biR, Fc gamma R, and p 150/95 were completely lost and the expression of CD1a and CD1c was markedly decreased or lost. Expression of molecules that have essential functions in antigen presentation remained present at the same level (MHC class II molecules and ICAM-1) or was markedly enhanced (LFA-3 and MHC class I). Highly remarkable was the dramatically enhanced expression of interdigitating cell marker RFD1. The monocyte/macrophage markers initially absent remained absent and the enzyme activity initially present (including ATPase and nonspecific esterase) remained present. In conclusion, the results in this report stress rapid alterations of human LC during in vitro culture, resulting in transformation into cells that have phenotypical characteristics of potent antigen presenting cells that resemble interdigitating cells.

Animals↗

Oral cyclosporin A in the treatment of psoriasis: an overview of studies performed in The Netherlands.

This is a review of the clinical studies performed so far in The Netherlands of the treatment of psoriasis with cyclosporin A (CyA), a selective immunosuppressive drug that has caused a major breakthrough in transplant medicine. Data derived from a double-blind placebo-controlled study (5 mg/kg/day of CyA), dose-finding studies (2.5 mg vs 5 mg/kg/day and 1 mg, 2 mg or 3 mg/kg/day), and long-term treatment of chronic plaque-type psoriasis (1.1-7.2 mg/kg/day) suggest an initial starting dose of 3 mg/kg/day irrespective of the severity of the disease. Long-term treatment brought about dose- and time-dependent (reversible) side-effects, including renal dysfunction and hypertension. Efforts to reduce the dose included concomitant administration of drugs known to have anti-psoriatic efficacy. Only combination with topical steroids appeared to add to the clinical efficacy of CyA, but did not allow a dose reduction sufficient to restore renal function. Dose reduction through intermittent treatment, however, postponed exacerbations sufficiently to permit at least partial normalization of serum creatinine levels. A similar effect was seen in the treatment of pustular palmoplantar psoriasis, which responded to doses of 1.1-6.1 mg/kg/day.

Administration, Oral↗

Analysis of side-effects of medium- and low-dose cyclosporin maintenance therapy in psoriasis.

The side-effects of long-term cyclosporin A (CyA) treatment in 26 patients with severe psoriasis were evaluated. These patients had a mean PASI score of 30.2 and were treated with CyA for between 7 and 37 months (mean 19.5 months). There were three groups according to the dose of CyA, less than 2 mg/kg per day, 2-3 mg/kg per day and greater than 3 mg/kg per day. In all three groups, CyA was found to be equally effective. Treatment with CyA was discontinued in 12 of the 26 patients because of nephrotoxicity and/or development of hypertension. One was in the less than 2 mg/kg per day group, three were in the 2-3 mg/kg per day group and eight in the greater than 3 mg/kg per day group. There was no hepatotoxicity with CyA treatment. One patient developed two squamous cell carcinomas of the skin.

Alkaline Phosphatase↗

Discoid lupus erythematosus-like lesions in carriers of X-linked chronic granulomatous disease.

A questionnaire was sent to 16 carriers of the X-linked cytochrome-b558 negative variant of chronic granulomatous disease (CGD). Of the 15 who answered the questionnaire and from data of one additional case, 70% reported recurrent aphthous stomatitis and 63% had recurrent skin eruptions. Five of the carriers (31%) had clinically discoid lupus erythematosus (DLE), although the histopathology was not typical and the immunofluorescence findings were negative. The infiltrate in the lesional skin of three of these patients was analysed using monoclonal antibodies against CD3, CD4, CD8, CDIa, HLA-DR, CDIc, interdigitating cells, B lymphocytes and cells of the monocyte/macrophage lineage. The immunophenotype of the infiltrating cells resembled that found in discoid lupus erythematosus.

Adolescent↗

Cyclosporin A levels in suction-blister fluid of patients with psoriasis treated systemically.

Oral cyclosporin A (CyA) is highly effective in the treatment of psoriasis. The long-term use is limited by dose-dependent side-effects, and the local concentration of CyA is a determining factor in treatment. The concentration of CyA in suction-blister fluid (SBF) and in whole blood was assessed using a polyclonal radioimmunoassay (RIA). This was carried out in patients with psoriasis following a single dose of CyA and while on adequate oral treatment with the drug. Peak blister fluid levels ranged from 32 to 170 ng/ml, and whole blood levels from 1250 to 2540 ng/ml. CyA trough levels (12 h following taking the drug) in the blister fluid ranged from 22 to 113 ng/ml, and in whole blood from 148 to 935 ng/ml. The trough concentrations in SBF were approximately 10% of whole blood trough levels.

Adult↗

Oral cyclosporin A is effective in clearing persistent pustulosis palmaris et plantaris.

In a prospective open study, seven patients with persistent pustulosis palmaris et plantaris were treated with oral Cyclosporin A (CsA). Clinical efficacy was assessed on a semi-quantitative 0-4 point scale for erythema, desquamation, induration and pustulation. CsA controlled skin lesions in doses ranging from 1.1 to 6.1 mg/kg body weight/day. Clinical side effects included renal impairment, nausea and tiredness. Rapid recurrence of the skin lesions was observed on withdrawal or insufficient treatment with the drug.

Administration, Oral↗

The restrictive role of sialic acid in antigen presentation to a subset of human peripheral CD4+ T lymphocytes that requires antigen-presenting dendritic cells.

Dendritic cells from human epidermis, i.e., Langerhans cells (LC), are more potent antigen-presenting cells (APC) than APC from peripheral blood in proliferative in vitro responses of helper T lymphocytes to various soluble antigens. Analysis of antigen recognition by CD4+ T lymphocyte clones indicated that this increased potency of LC as APC results from a preferential requirement for LC of part of the T cell population. These T cells show a long-lasting restoration of antigen responsiveness to peripheral blood APC after antigen-specific restimulation in vitro, indicating that restrictive antigen recognition concerns T cells that are not fully differentiated. A similar restrictive antigen recognition was observed by treatment of the T cells or the APC with neuraminidase. This restoration of responsiveness is associated with the occurrence of nonspecific cell clustering between T cells and APC. These results suggest that the selective requirement for APC is regulated by the function of adhesion molecules that are functionally blocked by sialic acid groups on immature peripheral T cells but that are readily available on peripheral T cells at a later stage of differentiation.

Antigen-Presenting Cells↗

Predominance of "memory" T cells (CD4+, CDw29+) over "naive" T cells (CD4+, CD45R+) in both normal and diseased human skin.

Absolute numbers of CD3+ T lymphocytes and their subpopulations were determined and statistically evaluated in the lesional skin of psoriasis, atopic dermatitis, nummular dermatitis, pityriasis rosea, and lichen planus. Skin sections were divided into horizontal layers and the numbers of CD3+ T cells as well as CD4+ inducer and CD8+ suppressor-cytotoxic T-cell subsets were counted. In addition, absolute numbers of the two subpopulations of inducer T cells, i.e., "memory" (4B4+ 2H4-) and "naive" (4B4- 2H4+) were evaluated. Unexpectedly, epidermal infiltration by T cells was highest in psoriasis and lowest in atopic dermatitis. In most cases, this exocytosis was dominated by CD8+ suppressor/cytotoxic T lymphocytes, with a minimal epidermal mean CD4/mean CD8 ratio of 0.04 in pityriasis rosea and a maximum of 0.48 in psoriasis. Inducer T cells within the epidermis were almost exclusively of the 4B4+ 2H4- "memory" T-cell subpopulation, whereas 4B4- 2H4+ "naive" T cells were extremely uncommon in lesional epidermis. Similar results were obtained for dermal T cells in all diseases studied, i.e., 4B4- 2H4+ "naive" T cells were relatively rare. Papillary dermis infiltration by T cells was highest in lichen planus where a mean CD4/mean CD8 ratio of 1.10, the minimum in this comparative study, was obtained. The mean CD4/mean CD8 ratio of the papillary infiltrate was highest in atopic dermatitis (4.12). Our results indicate disease-specific and significantly different infiltration patterns of T-lymphocyte subsets in the chronic inflammatory dermatoses investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

Increased anthralin irritation response in vitiliginous skin.

The irritation response to anthralin was studied using the chamber-testing technique in 17 patients with vitiligo. Anthralin concentrations of 0.1%, 0.5%, 1%, and 5% in lanette wax were applied to both vitiliginous and adjacent pigmented skin for 24 h. The extent of the erythematous reaction was evaluated on the 2nd day after application. The visual assessment of the paired anthralin patches indicated that the erythema was more intense in pigmented skin than in vitiliginous skin in 15 out of 17 patients. Chromometer readings, however, clearly indicated that the erythematous response was stronger in the vitiliginous skin than in the pigmented skin, confirming the known fact that the human eye is not accurate in the quantitative assessment of complex colors. Immunophenotypification of cellular infiltrates, using the combination of different monoclonal antibodies and the peroxidase technique, showed that inflammatory cell infiltrates caused by the anthralin exposure contained increased numbers of granulocytes and monocytes in vitiliginous skin when compared with normal skin. The percentage of T-cell subsets, Langerhans cells, and mast cells in the same infiltrates of both types of skin were similar. Our results are discussed in accordance with the view that anthralin-induced radical species of the pigmented skin can be neutralized by the scavenging properties of melanin.

Adult↗

An improved model for tissue expansion and flap research in the rabbit.

A pocket for tissue expander implantation in the rabbit is described at the level between the skin and the panniculus carnosus. The vascular anatomy of the undermined skin was studied with microangiography which showed a functional (sub)dermal plexus. Expanders were placed in seven rabbits and inflated daily over a period of 10 days. Blood flow in expanded skin, as measured with laser Doppler flowmetry, dropped with increasing inflation pressure. During the course of expansion, the intraluminal pressure returned to a baseline level within 24 hours after each inflation. It is concluded that an expander placed in the described layer in the rabbit causes considerable skin stretch and interferes with cutaneous blood supply and is therefore an improved model for tissue expansion in the human.

Animals↗

Quantification and distribution of lymphocyte subsets and Langerhans cells in normal human oral mucosa and skin.

Normal human oral (check) mucosa was studied to discover whether the oral cavity resembles the Mucosal Immune System (MIS) or the Skin Immune System (SIS). Immunophenotypes of lymphocyte subsets and Langerhans cells (LC) with their exact locations in the epithelium and papillary layer of the normal buccal mucosa were determined and compared with data of normal human skin. In a double staining procedure, the distribution of T-lymphocytes in relation to blood and lymph vessels was determined. Immunophenotyping of LC was done with a CD1a monoclonal antibody. In contrast to the skin, T-lymphocytes in buccal mucosa are not primarily perivascular in location. They are more or less randomly distributed on both sides of the basement membrane. The epithelium of the buccal mucosa contains about 37 times as many T-lymphocytes as the epidermis of normal skin. T-cell numbers in the papillary layer are more or less comparable. The CD4/CD8 ratios of about 1/2 in the epithelium of buccal mucosa and 1/4 in the skin indicates preferential presence of the CD8 subset in both sites, but the helper/inducer T-lymphocytes play a much greater role in the epithelium of the buccal mucosa when compared with skin. B-lymphocytes were not found in the epithelium and papillary layer of the buccal mucosa. Thus, immune response associated cells in buccal mucosa do not show the MIS pattern since B cells are absent. It has more in common with SIS but differences are also apparent. In the epithelium of the buccal mucosa the density of LC does not differ significantly from that of the skin, but the papillary layer of the buccal mucosa contains significantly fewer LC than the skin. As in the skin most of the LC of the buccal mucosa are found in the epithelium.

Adult↗

The poikiloderma of Rothmund-Thomson syndrome: changes in Langerhans cell morphology and distribution.

A black girl with the Rothmund-Thomson syndrome is presented. Immunophenotyping of subpopulations of immunocompetent cells in a biopsy of an atrophic hyperpigmented skin lesion revealed sparsity and unusual distribution of epidermal Langerhans cells. These cells were mainly located in the basal layer of the epidermis and did not show the usual dendritic pattern. Impressive immunoreactivity of the dermal infiltrate was observed by anti-HLA-DR staining. The changes in Langerhans cell morphology and distribution may indicate functional impairment of the up-regulating arm of skin immunity.

Child, Preschool↗

Antibodies against ocular and oral antigens in Behçet's disease associated with uveitis.

An indirect immunofluorescence test (IIF) using guinea pig lip as a substrate was performed with sera from 10 patients with Behçet's disease and the results were compared to IIF with sera of 16 patients with uveitis of Turkish origin, 62 patients with non- Behçet's uveitis, 9 patients with stomatitis aphtosa and 34 healthy controls. Antibodies to guinea pig lip cytoplasmic antigens were present in 70% of the Behçet patients, in 19% of uveitis patients of Turkish origin (P less than 0.05), in 12% of the non Behçet uveitis patients (P less than 0.001), in 11% of the stomatitis aphtosa patients (P less than 0.05) and in 9% of the healthy controls (P less than 0.001). A positive Behçet serum preincubated with the supernatant of guinea pig lip sections incubated in PBS gave an inhibition on the IIF test, indicating that the antigen involved in a soluble cytoplasmic substance. No significant increase in the presence of antibodies against iris, cornea or retina (mouse eye) were detected in the Behçet sera. Of interest was the finding of a positive reaction in 6 out of 10 patients in the episcleral region of the mouse eye. This positive reaction resembles immune complex like material. Our findings suggest that using the external surface of the guinea pig lip as a substrate is useful in selecting out those patients with Behçet's disease from uveitis patients with an unknown etiology and from patients with aphtous stomatitis.

Adult↗

The selective antigen-presenting cell capacity of activated B lymphocytes in HLA-II-restricted responses of CD4+ T lymphocytes.

We examined the role of antigen-presenting B lymphocytes using panels of antigen-specific CD4+8-T-lymphocyte clones (TLC). All 19 TLC showed a class II major histocompatibility complex-encoded (HLA-II) restricted proliferation to antigen presented by antigen-presenting cells (APC) from the monocyte fraction of peripheral blood. Only six TLC were effectively activated by antigen presented by autologous B lymphocytes activated by EBV transformation. This failure of B lymphocytes was not due to: (i) a high degree of cell surface sialic acid; (ii) a low expression of the cell surface proteins HLA-II, ICAM-1 or LFA-3 that restrict antigen presentation; (iii) lack of secretion of the cytokine IL-1 or other soluble factors that may be required as secondary signals; or (iv) induction of incomplete T-cell activation resulting in the production of growth factor interleukin-2 (IL-2) or the expression of receptors for IL-2 only. These data suggest the involvement of another cell surface interaction in antigen presentation acting besides the interactions known so far.

Antigen-Presenting Cells↗

Allergic contact dermatitis in children and young adults.

We evaluated the results of a 5-year period of epicutaneous testing in children and teenagers younger than 16 years of age. In an overall-tested population of 2671 persons, 67 were younger than 16 years. In 16 (23.8%) of these 67 children, a positive epicutaneous test was considered to be clinically relevant for the diagnosis allergic contact dermatitis. From the total of 44 positive tests, the most common allergen was nickel sulfate (18%), followed by balsam of Peru, Carba mix, colophony, and fragrance mix (6% each). As our test population consisted of only a few children, no conclusions were drawn in respect to children younger than 10 years. Despite our careful selection of children with allergic contact dermatitis, the prevalence of positive epicutaneous tests was no different than that reported for unselected populations of children.

Adolescent↗