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Biomedical subjects

A Scheynius

Publications and source records attributed to A Scheynius.

At least 55 records · Page 3Linked to original sources
PubMed1992

In vivo treatment with interferon-gamma during early pregnancy in mice induces strong expression of major histocompatibility complex class I and II molecules in uterus and decidua but not in extra-embryonic tissues.

Allopregnant (NFR/N [Swiss-derived] H-2q females x 57/Bl H-2b males) and syngeneically pregnant (NFR/N x NFR/N) mice were subjected to daily injections (10(5) U/mouse/day, from Day 5.5 of gestation) of recombinant rat or mouse interferon-gamma (IFNg) in order to investigate its ability to induce extra-embryonic major histocompatibility complex (MHC) expression and antipaternal immune reactions if administered during the first part of the gestation period. In addition, a limited number of IFNg-treated embryo-transferred NFR/N mice carrying C57/B1 embryos (representing a complete allogenic pregnancy) were investigated. Mouse and rat IFNg caused the same type of histological and physiological changes, and most of the experiments were performed by using rat IFNg. Several IFNg-treated mice (irrespective of type of mating) showed a drop in weight and a high rate of resorptions at Day 12.5 of gestation. This interference with pregnancy appeared not to be caused by immunological reactions against the feto-placental unit (no leukocyte infiltration and no significant effect on serum levels of antipaternal antibodies in preimmunized allopregnant IFNg-treated mice). Immunohistochemical stainings of cryosectioned tissues at Day 9.5 of pregnancy revealed that IFNg treatment caused a strong induction of MHC class I and class II expression on most cells in the uterus and on several cells in the maternal decidua, while there was a complete absence of detectable MHC class I and class II expression in the extra-embryonic tissues. Characteristic for a Day 12.5 placenta of an IFNg-treated mouse (including embryo-transferred mice) was a strongly MHC class II-induced maternal decidua and a completely MHC class II-negative fetal placenta. The pattern of IFN-induced MHC class I expression was similar to that of class II, with the exception of class I expression on scattered cells within the basal zone. Thus, the present study provides immunohistological evidence that IFNg administered in vivo during the first part of gestation is not capable of inducing MHC expression on murine extra-embryonic cells despite an extremely high expression of MHC molecules on decidual cells in intimate contact with extra-embryonic tissues. It is likely that the resistance to IFNg-mediated induction of MHC expression on extra-embryonic cells is of basic importance for the protection of mammalian semi-allogeneic fetuses.

Animals↗
PubMed1992

Expression of interferon-gamma receptors in normal and psoriatic skin.

Psoriatic keratinocytes have a reduced antiproliferative response to interferon (IFN)-gamma, and HLA-DR expression is usually not observed on keratinocytes in psoriatic plaques despite the presence of activated T cells. We have therefore compared the expression of IFN-gamma receptors in psoriatic skin with that of normal human skin. Using mouse monoclonal antibodies and immunoperoxidase staining on cryostat cut sections, we detected IFN-gamma receptors on keratinocytes throughout the epidermal layers except stratum corneum in normal skin (n = 11). Biopsy specimens from involved psoriatic skin (n = 17) consistently showed a staining pattern that differed from that of normal skin in that only the lower part of epidermis reacted with the antibodies to IFN-gamma receptors, whereas the upper layers showed no or minimal staining. Expression of IFN-gamma receptors in uninvolved psoriatic skin (n = 16) did not differ from that of healthy controls. Forty-five percent of the biopsies from lesional psoriatic skin displayed ICAM-1 positive keratinocytes, and only two specimens had a limited expression of HLA-DR reactive keratinocytes. The decreased binding of antibodies against the IFN-gamma receptors in the upper part of psoriatic epidermis might be secondary to abnormal maturation of psoriatic keratinocytes or a primary defect involving abnormal modulation of IFN-gamma receptors.

Adult↗
PubMed1992

Localization of allergens in the domestic mite Lepidoglyphus destructor.

The non-pyroglyphid domestic mite Lepidoglyphus destructor is a major source of allergen causing respiratory symptoms in farming environments. This study is the first to focus on the localization of the allergens in the non-pyroglyphid domestic mite Lepidoglyphus destructor. Cryostat-cut sections of L. destructor mite bodies and faecal pellets were probed with one of three mouse monoclonal antibodies (MoAbs) raised against L. destructor or with patient sera, and stained with immunoperoxidase. Eight sera were RAST-positive to L. destructor and L. destructor faecal pellets. These eight RAST-positive patient sera labelled the wall of the L. destructor gut and two of them also the faecal pellets. The MoAbs additionally labelled parts of the exoskeleton and reacted with a majority of the faecal pellets. Cryostat-cut sections of Dermatophagoides pteronyssinus mite bodies and faecal pellets were probed with L. destructor MoAbs, which resulted in only slight staining of a few faecal pellets. The results suggest that at least one L. destructor allergen is associated with digestion.

Adult↗
PubMed1992

Quantitative analysis of Langerhans' cells in epidermis at irritant contact reactions using confocal laser scanning microscopy.

Confocal laser scanning microscopy (CLSM) was used for quantitative analysis of CD1a+ cells in epidermis at irritant reactions. Sodium lauryl sulphate (2% and 4%) or non-anoic acid (20% and 80%) were applied to the skin of healthy volunteers under occlusion for 24 h. Skin biopsy specimens were taken after additional 24 h and were snap frozen. Freeze-sections, 25 microns thick, were stained with anti-CD1a antibodies (Leu-6) followed by FITC-labelled rabbit anti-mouse IgG. The sections were viewed and optically sectioned in the CLSM at four depth levels. The data was analysed using a threshold value for the fluorescence. The obtained result is presented as the proportion of specimen area having a fluorescence intensity above the threshold. The result demonstrates that the CLSM is a useful tool for obtaining not only structural information but also quantitative information from a defined tissue volume. In the present investigation it was possible to demonstrate variations in CD1a+ reactivity in epidermis at detergent-induced irritant reactions with a marked decrease in CD1a+ after 80% non-anoic acid exposure and only minor differences in the CD1a+ after 2% and 4% sodium lauryl sulphate exposure.

Cell Count↗
PubMed1991

Placental MHC class I antigen expression is induced in mice following in vivo treatment with recombinant interferon-gamma.

Allogeneically pregnant mice (NFR/N (Swiss-derived) H2q x 57/B1 H2b) were injected daily from day 11 to 18 of gestation with recombinant rat interferon-gamma (IFN-gamma) and the effects on placental MHC antigen expression were evaluated by immunohistochemistry. The results demonstrated that a daily dose of 200,000 U/mouse induces a significant increase in placental MHC class I expression in the decidua and the basal zone spongiotrophoblast as well as the fetal mesenchyme, while the labyrinthine trophoblast was almost completely MHC negative. No significant induction of MHC class II antigen expression was observed in the placental tissue, with the exception of a few scattered cells. The MHC class II-inducing efficiency of the treatment protocol used was ascertained by staining maternal skin (ear), which proved to contain considerably elevated numbers of MHC class II-positive cells (mainly keratinocytes). The IFN-gamma treated group showed a higher incidence of fetal resorptions than the corresponding controls, but this was probably due to a non-specific toxic effect of the treatment as none of the sera analysed contained detectable amounts of anti-paternal antibodies, no infiltrating lymphocytes were detectable on histological examination of placental sections, and most of the IFN-gamma treated animals successfully completed their pregnancy.

Animals↗
PubMed1991

Interleukin-1-like activity in normal rat skin after in vivo treatment with interferon-gamma.

The influence of interferon-gamma (IFN-gamma) on immune responses is still ambiguous. We have investigated whether IFN-gamma influences the constitutive interleukin-1 (IL-1)-like activity in normal rat skin because IL-1 is a regulatory cytokine in immune responses. Rats were injected intradermally into both ears with different doses of rat recombinant IFN-gamma (10(3)-10(5) U), and control animals were given phosphate-buffered saline (PBS). The animals were killed at different times and the ears were cut off at the bases. The biologic activity of the IFN-gamma was verified by immunohistochemistry on injected ears, showing a time- and dose-dependent induction of major histocompatibility complex class II antigens on the keratinocytes. Aqueous extracts of homogenized ear skin were tested for IL-1-like activity in a mouse thymocyte bioassay. No major effects of IFN-gamma on the constitutive IL-1-like activity in the rat skin were found; at 6 h there was a slight reduction and at 72 h an increase in IL-1 bioactivity in extracts from IFN-gamma (10(5) U)-injected animals compared with PBS-treated controls (p less than 0.05). We conclude that the regulation of immune responses in the rat skin by IFN-gamma is less likely to be mediated via changes in the IL-1-like activity.

Animals↗
PubMed1991

An immunological study in patients with seborrhoeic dermatitis.

The humoral and cellular immune-status was studied in 30 patients with seborrhoeic dermatitis. Increased frequencies of natural killer cells were found in 46% of patients. Furthermore, subnormal mitogen stimulation responses were demonstrated in 13 patients, whereas two individuals were found to have very high numbers of activated T lymphocytes in peripheral blood. Higher-than-normal total serum IgG and IgA was observed in 14 and 11 patients, respectively. For nine of 12 patients with skin lesions, dermal perivascular cell infiltrates were seen. The majority of the infiltrating cells reacted with anti-CD4 antibodies. HLA-DR-expressing keratinocytes were found in two biopsies. The study suggests that patients with seborrhoeic dermatitis may have depressed T-cell function. This could have a bearing on their susceptibility to the Pityrosporum ovale-associated dermatitis. The very high frequencies of activated T cells observed in the peripheral blood of two otherwise healthy seborrhoeic individuals suggests that intermittent systemic immune activation may occur. Seborrhoeic dermatitis is a common skin disease. It can be diagnosed by its characteristic red to yellow-brown lesions covered with greasy scales distributed in areas with a high number of sebaceous glands, such as the scalp, face and upper trunk. There is an association between seborrhoeic dermatitis and the lipophilic yeast Pityrosporum ovale but its exact aetiological role is not known. The yeast is a member of the normal cutaneous flora but also the aetiological agent of pityriasis versicolor and Pityrosporum folliculitis. P. ovale can activate complement via the direct and alternative pathways. This may play some part in the induction of inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

The evaluation of various methods and antigens for the detection of antibodies against Pityrosporum ovale in patients with seborrhoeic dermatitis.

Sera from 10 patients with seborrhoeic dermatitis and from 10 age-matched healthy individuals were examined for IgG activity against Pityrosporum ovale. The IgG activity was analysed using the following techniques: an enzyme-linked immunosorbent assay (ELISA) against whole P. ovale cells, purified cell-wall carbohydrate or protein extract, an indirect slide-immunofluorescence assay and fluorescence-activated flow cytometry using the whole organism as antigen. The ELISA method using the protein antigen was the only technique that showed a significant difference between patients and controls; a lower antibody response was found in the seborrhoeic dermatitis patients compared to healthy controls.

Adult↗
PubMed1991

Gastric epithelial cells in Helicobacter pylori-associated gastritis express HLA-DR but not ICAM-1.

Induced expression of the intercellular adhesion molecule 1 (ICAM-1) and of the major histocompatibility complex (MHC) class II antigens has been simultaneously observed on keratinocytes and epithelial cells in the thyroid and kidney, suggesting that ICAM-1 and HLA-DR expression might be under common regulation. We have previously found an association between the presence of Helicobacter pylori and an induced expression of class II antigens on gastric epithelial cells in gastric biopsy specimens from patients with gastritis. In this study we investigated whether ICAM-1 could also be expressed on the gastric epithelium. Thirty-one patients with clinical indications for upper gastrointestinal endoscopy were examined. In 23 patients gastritis was diagnosed endoscopically and histologically and H. pylori was cultured from biopsy specimens. In eight patients neither histological gastritis nor growth of the bacteria was observed. Immunoperoxidase staining demonstrated expression of HLA-DR but not ICAM-1 on the gastric epithelial cells in all patients with H. pylori-associated gastritis, indicating regulatory mechanisms different from those of other epithelial cells.

Adult↗
PubMed1991

Intravenous or cold ex vivo administration of monoclonal antibodies for conditioning of rat small-bowel allografts.

The following study describes cold ex vivo or intravenous infusion of monoclonal antibodies (MCAB) for lymphocyte target cells of rat small-bowel grafts. The MCAB Ox8, directed against CD8+ T lymphocytes, is used here as a model antibody. We demonstrate that Ox8 antibodies administered during cold ex vivo perfusion are able to reach the target cells in the small-bowel mucosa and the mesenteric lymph nodes of rat small-bowel grafts. Thus, cold perfusion of the vascular system for 20-60 min resulted in good labelling of the CD8+ T cells as analysed on cryostat tissue sections using immunoperoxidase staining. Rats treated with Ox8 intravenously 60 min before taking of specimens showed similar labelling. Additional staining of the tissue sections with Ox8 antibody resulted in no further labelling, thus indicating that nearly all CD8+ T cells were labelled both after ex vivo perfusion and after intravenous treatment of the donor. It is concluded that MCAB can, as an alternative to the intravenous route, be administered ex vivo after organ harvesting.

Animals↗
PubMed1991

Multiple epitopes on cartilage type II collagen are accessible for antibody binding in vivo.

Monoclonal mouse antibodies specific for the major epitopes on mouse type II collagen (CII) were biotinylated and injected into neonatal and adult mice. Anti-CII antibodies, specific for four different epitopes on the CII molecule, could be shown to bind specifically to joint surfaces in the paws of 2-day-old syngeneic DBA/1 mice after an intraperitoneal injection of 100 micrograms of biotinylated antibody. The anti-CII antibodies did not bind to cartilage from DBA/1 mice in vitro, unless the sections were pretreated with hyaluronidase or the specimens decalcified prior to freezing, showing that the epitopes are accessible in vivo but not in vitro. By analyzing the in vivo binding capacity for a number of monoclonal anti-CII antibodies which represented different IgG subclasses, it could be demonstrated that binding to the same epitopes occurred independent of IgG subclass. However, one epitope (denoted "B1") was only weakly detected, possibly due to the fact that the antibody used (CIIB1) crossreacts with type I collagen and C1q. Monoclonal anti-CII antibodies, injected into neonates or adult mice, bound specifically to most, but not all, tissues containing CII; including hyaline joint cartilage, fibrous sternal and costal cartilage, tracheal cartilage and fibrous cartilage in the spine but not to CII-containing structures in the eye. The finding that CII, while present in cartilage, is accessible for antibody binding in vivo may have important implications for the availability of CII for the immune system and for the understanding of the development of pathological autoimmunity leading to collagen-induced arthritis in mice.

Animals↗
PubMed1991

An increased number of gamma/delta T-cells and gastric epithelial cell expression of the groEL stress-protein homologue in Helicobacter pylori-associated chronic gastritis of the antrum.

Numerous studies have shown that the presence of Helicobacter pylori in the stomach is linked to the development of chronic gastritis most commonly seen in the antrum. However, the pathogenic mechanisms are unclear. In 23 of 31 patients, examined due to symptoms from the upper gastrointestinal tract, H. pylori-associated chronic gastritis of the antrum was diagnosed histologically and by growth of H. pylori. Immunoperoxidase staining on gastric biopsy specimens from these patients showed an increased number of gamma/delta T-cells within the epithelium. Furthermore, the Mab ML30 (raised against the 65 kDa heat shock protein of mycobacteria) demonstrated positive staining in the gastric epithelial cells in all H. pylori-positive but not in H. pylori-negative biopsy specimens. H. pylori also reacted with ML30, as detected by immunoperoxidase staining as well as by immunoblotting. Intraepithelial gamma/delta T cells may play a role in host defense against invading H. pylori, and the bacteria may trigger an autoimmune response to stress proteins expressed by the gastric epithelial cells.

Adult↗
PubMed1991

Differential effects of sodium lauryl sulphate and non-anoic acid on the expression of CD1a and ICAM-1 in human epidermis.

Normal human skin was exposed to two different detergents, sodium lauryl sulphate in distilled water and non-anoic acid in isopropanol at different concentrations. The detergents were applied under occlusion in epicutaneous tests for 24 h and biopsies were taken at 24 or 48 h. Frozen sections were labelled with monoclonal antibodies against CD1a, CD3 and ICAM-1. The evaluation of the labelled sections showed that there were differential effects on the expression of ICAM-1 and CD1a+ cells in epidermis. After non-anoic acid application ICAM-reactivity could not be detected and there was a decrease of staining for CD1a after exposure to 80% non-anoic acid. Sodium lauryl sulphate treatment, however, induced ICAM-1 expression on keratinocytes and had minor effects on the number of CD1a+ cells. ICAM-1 expression was also detected in normal epidermis in 3 of 9 unexposed control biopsies and after occlusion with the vehicles distilled water and isopropanol. An increased amount of CD3+ cells was found in the skin exposed to both detergents. The results show that there are dose and time dependent variations in the epidermal response to irritants which might influence the immunological events taken place in the epidermis.

Adult↗
PubMed1991

Alveolar accumulation of hyaluronan and alveolar cellular response in bleomycin-induced alveolitis.

Hyaluronan (HA) accumulating in the alveolar interstitial tissue of rats injured by a single intratracheal instillation of bleomycin has been visualized histologically and assayed. HA was present already by Day 1 after bleomycin treatment, increased to a maximum value on Days 3 and 7 and then declined. A time-dependent relationship between this early connective tissue response and the invasion of inflammatory cells in the alveolar tissue was apparent. The dominating invading cells by Day 1 were granulocytes showing positive staining for the monoclonal antibody OX-42 reflecting the C3b receptor. The numbers of macrophages expressing class II antigens started to increase on Day 1, reaching a maximum on Days 3-7 and then declined. Macrophages were the dominating OX-42+ cells by Day 7. The appearance of W3/13+ cells ("pan-T-lymphocytes") showed a similar pattern to that for the class II expressing macrophages. The number of cells expressing CD4 antigen increased until Day 3 and levelled off on Day 30 whilst the largest number of cells expressing CD8 antigen was seen on Day 30. Few cells expressing B-cell phenotype outside lymph nodules were identified. Alveolar lining epithelial cells, probably epithelial type II cells, expressed class II antigens by Days 3-14. The time-related accumulation of HA and the appearance of T-cells, macrophages and granulocytes expressing signs of activation suggests that these cells may be involved in the early connective tissue response of the lung injured by bleomycin.

Animals↗
PubMed1990

Increased expression of platelet-derived growth factor type B receptors in the skin of patients with systemic sclerosis.

The expression of B-type receptors for platelet-derived growth factor (PDGF) was investigated in skin biopsy samples from patients with systemic sclerosis (SSc), by immunohistochemical staining using monoclonal antibodies specific for the receptor. Whereas skin from healthy individuals lacked expression of PDGF-B receptors, receptor expression was seen in sclerodermatous skin lesions from 13 of 14 patients. Increased receptor expression was observed in dermal vessels, as well as on many stromal fibroblast-like cells close to these vessels. PDGF-B receptor expression was most pronounced within and around dermal vessels in which perivascular infiltrates of Leu-4-positive T lymphocytes and HLA-DR-positive, RFD7-positive activated macrophages were present. Both perivascular inflammatory cell infiltrates and PDGF-B receptor expression were generally also seen in macroscopically normal areas of the skin of the SSc patients, indicating that the observed phenotypic alterations may precede the macroscopically observable features of scleroderma in the skin. The observed induction of PDGF-B receptors, together with indirect indications of increased synthesis and release of PDGF, would be compatible with altered PDGF-mediated control of connective tissue cell growth as part of the molecular basis for development of the skin lesions in SSc.

Adult↗
PubMed1990

Effects of interferon-gamma treatment on the cutaneous DTH reaction in rats.

The capacity of interferon-gamma (IFN-gamma) to induce class II histocompatibility antigens on different cell types including keratinocytes, is well known, but the impact of IFN-gamma on the immune response is still unclear. Lewis rats sensitized with dinitrofluorobenzene (DNFB) were injected with recombinant rat IFN-gamma (10(5) U) or phosphate-buffered saline (PBS) once daily on 3 successive days at the bases of the ears either before or after they were challenged on the ears. As expected, the PBS-treated animals showed about a 30% increase in ear thickness and there was an induced expression of class II antigens on the keratinocytes as judged by immunohistochemistry 72 h after challenge. Exogenously added IFN-gamma prior to DNFB challenge resulted in a significantly reduced ear swelling at 24 (p less than 0.01) and 48 h (p less than 0.05) after challenge. In this case the keratinocytes expressed class II antigens already at the time of challenge. When IFN-gamma injections were given during the contact allergic reaction there was no significant reduction of ear swelling until 72 h (p less than 0.01). At that time point there was a more pronounced expression of class II antigens on the keratinocytes compared with PBS-injected animals, due to the IFN-gamma treatment. These in vivo data support our previous observations that IFN-gamma may play a self-limiting role in certain immune responses.

Animals↗
PubMed1990

Three-dimensional visualization of human Langerhans' cells using confocal scanning laser microscopy.

Most techniques used to visualize cells in tissues are accompanied by some distortion of the tissue due to fixation and sectioning. We here present a technique involving "optical sectioning" and three-dimensional reconstruction of fluorescence-labelled Langerhans' cells in human skin that avoids such problems. The instrument used to study the specimens was a PHOIBOS Confocal Scanning Laser Microscope (CSLM) built around a Zeiss Universal microscope. A software package for three-dimensional reconstructions of confocal sections was employed for calculations in a Hewlett-Packard HP9000-350 minicomputer running UNIX. Normal human skin obtained at plastic surgery or skin biopsy specimens from allergic, irritant, or control patch test reactions was studied. Epidermis separated from dermis by incubation in thermolysin or thick (25 microns) cryostat sections were incubated with fluorescein-isothiocyanate labelled mouse monoclonal antibodies directed against HLA-DR. To reduce the fading of immunofluorescence during microscopy, the specimens were mounted with glycerol in PBS containing p-phenylenediamine. The results indicate that CSLM is a powerful tool for investigations on Langerhans' cells in different conditions of the skin allowing a three-dimensional view of cells in unfixed or acetone-fixed preparations at the light microscope level.

Fluorescent Antibody Technique↗