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Biomedical subjects

A Scheynius

Publications and source records attributed to A Scheynius.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1990

Immunomorphology of graft-versus-host disease after small bowel transplantation in the rat.

The process of graft-versus-host disease (GVHD) elicited by small bowel semi-syngeneic grafts in Lewis rats was studied by an immunohistochemical staining technique for analysis of MHC (major histocompatibility complex) class II antigen expression and of T-cell subpopulations in different organs. Specimens from the graft, native bowel, brain, testis, liver, kidney, and skin were taken on days 5, 10, and 15. All the investigated organs displayed strong class II antigen induction during the course of GVHD. In the native bowel of semi-syngeneically transplanted animals, only discrete morphological changes were noted, whereas the graft displayed a generalized serosal reaction with large infiltrates of rounded and polygonal cells expressing class II antigens. This was not observed in the graft of syngeneically transplanted animals. In the lamina propria of the semisyngeneic graft, 'free' lymphocyte-like cells were depleted and, at the same time, localized aggregates of these cells were observed. Crypt cell class II expression in the native bowel, and to some extent in the graft, was increased during GVHD. However, pronounced intraindividual variations in MHC class II antigen expression were noted, and class II expression was therefore not considered to be a good marker for GVHD.

Animals↗
PubMed1990

Inoculation of barrier-born pigs with Helicobacter pylori: a useful animal model for gastritis type B.

At the age of 8 weeks, 15 barrier-born pigs, specific pathogen free, were inoculated intragastrically with suspensions of 10(7) to 10(10) CFU of Helicobacter pylori after pretreatment with omeprazole. The pigs were observed for up to 12 weeks, endoscopic biopsy specimens were taken, and serum samples were drawn. H. pylori was identified by routine culturing and by staining with an H. pylori-specific monoclonal antibody on cryostat sections of gastric biopsy specimens. In 11 of 15 inoculated pigs, H. pylori was detected throughout the observation period. In these infected pigs, there was an antibody response to H. pylori, as determined in serum by an enzyme immunoassay. Furthermore, the development of superficial, focal gastritis with infiltrates of mononuclear class II antigen-expressing lymphocytes was observed immunohistologically. H. pylori was never detected and an antibody response to H. pylori was not observed in two control pigs. The development of gastritis and the systemic antibody response to H. pylori support the usefulness of this animal model for studies of H. pylori-related human diseases.

Animals↗
PubMed1990

Antipruritic effect of oral cyclosporin A in atopic dermatitis.

The effect of ten days' treatment with cyclosporin A, 5 mg/kg/day, in 10 adults with atopic dermatitis was investigated using a double-blind, randomized, placebo-controlled, cross-over design. Evaluation was based on itch recording, clinical scoring and immunohistochemical examination of skin biopsy specimens. Cyclosporin A significantly reduced the itch intensity, the eczema score and the consumption of topical hydrocortisone. A significant decrease in serum magnesium and in the total number of blood eosinophils was seen. No other laboratory abnormalities were observed. In lesional skin, Cyclosporin A induced a relative decrease of CD3+ T cells in 5/10 patients, of HLA-DR+ cells in 6/10, and of interleukin-2-receptor positive (CD25+) cells in 4/10. However, these changes in phenotype expression did not seem necessary for itch relief. Relapse of clinical symptoms was seen within 2-30 days of completion of the Cyclosporin A course. The mechanism of the antipruritic effect remains unclear, but the present findings may support the hypothesis that 'pruritogenic cytokines', whose production is inhibited by Cyclosporin A, may be important in the pathogenesis of itch in atopic dermatitis.

Administration, Oral↗
PubMed1989

Induction of mRNA for HLA-DR beta in human keratinocytes cocultured with interferon-gamma.

Explanted human keratinocytes exposed in vitro to recombinant interferon-gamma (IFN-gamma) were investigated for the appearance of mRNA for HLA-DR. Using in situ hybridization with a (35S)UTP-labelled HLA-DR beta cRNA probe, mRNA-positive cells were detected already within 6 h with maximal numbers of positive cells as well as the amount of mRNA per cell after 48 h. The corresponding protein HLA-DR, as analysed by immunoperoxidase staining, was detected on 20%-40% of the cells after 24 h and on almost all cells within 48 h. The expression of HLA-DQ and -DP antigens were always exceeded by that of HLA-DR. Whereas an increase in the concentration of IFN-gamma above 50 U/ml did not affect the maximal level of HLA-DR reactive cells, there was a fourfold increase in the frequency of cells reactive with HLA-DQ and a twofold increase for HLA-DP when the IFN-gamma concentration was raised from 50 to 500 U/ml. When IFN-gamma was withdrawn from the cultures, HLA-DR mRNA and protein synthesis ceased--indicating the continuous need for IFN-gamma to maintain the HLA-DR synthesis in keratinocytes.

DNA↗
PubMed1989

Effects of purified protein derivative (PPD)-activated syngeneic epidermal cells on a PPD-specific rat T-helper cell line.

An important question in local immune regulation in the skin is how keratinocytes at inflammatory sites can modify a local T-cell response to antigens introduced via the skin. In the present study we investigated the effects of rat epidermal cells obtained from the site of a tuberculin reaction, on the proliferative response of a syngeneic purified protein derivative (PPD)-specific CD4+ T-cell line. Epidermal cell suspensions from the tuberculin-reactive ears contained 23-37% cells expressing class II transplantation antigens as judged by immunocytochemistry compared with 2-3% in normal epidermis. When comparing the capacity of these two different epidermal cell populations to induce a PPD-specific T-cell response in vitro, it was found that the PPD-reactive epidermal cells induced a lower T-cell response than did normal epidermal cells. This discrepancy cannot be explained by an infiltration of inflammatory cells into the epidermis of tuberculin-reactive ears. Our data indicate that epidermal cells modified during a delayed-type hypersensitivity reaction in vivo may suppress an antigen-specific T-cell proliferation.

Animals↗
PubMed1989

Association of Campylobacter pylori with induced expression of class II transplantation antigens on gastric epithelial cells.

Campylobacter pylori was identified with immunoperoxidase staining and a mouse monoclonal antibody directed against C. pylori in gastric biopsy specimens from 24 patients with gastritis. C. pylori was not found in gastric biopsy specimens from six subjects with histologically normal mucosa. The monoclonal antibody, which was reactive with a surface protein of approximately 20 kilodaltons, was found to be specific for C. pylori, and the immunoperoxidase staining proved to be more sensitive and rapid than culture in detecting the organism. In the tissue specimens where C. pylori was detected with the monoclonal antibody, there was a strong expression of class II transplantation antigens on the epithelial cells and an increased number of T lymphocytes. These findings indicate that C. pylori may initiate local immune responses.

Antibodies, Monoclonal↗
PubMed1989

Effects on rat T-helper cell proliferation by syngeneic epidermal cells exposed to IFN-gamma in vivo.

In several conditions in the skin, characterized by T-cell infiltration, keratinocytes are induced to synthesize and express class II transplantation antigens. The biological significance of this induced expression is still not understood. In this study, class II antigens were induced on rat ear keratinocytes by local intradermal injections into the ear of rat recombinant interferon-gamma (IFN-gamma). Epidermal cell suspensions prepared from these ears contained more than 50% class II-expressing cells, as judged by immunocytochemistry, compared with less than 5% in untreated epidermis. When comparing the capacity of these to different epidermal cell populations to stimulate a syngeneic PPD-specific T-helper cell line, it was found that IFN-gamma-exposed epidermal cells induced a lower T-cell response to PPD than did normal epidermal cells. This discrepancy could not be explained by either an infiltration of inflammatory cells into the epidermis of IFN-gamma-treated ears or by a difference in interleukin-1 production as determined in culture supernatants. The addition of indomethacin to cultures with IFN-gamma-exposed epidermal cells restored the T-cell response to PPD to that of normal epidermal cells, suggesting an inhibitory effect of prostaglandins. Our data indicate that epidermal cells exposed to IFN-gamma in vivo can suppress an antigen-specific T-cell proliferation.

Animals↗
PubMed1989

Immunohistochemical reactivity of monoclonal antibodies generated after immunization of mice with cells from a psoriatic lesion.

Monoclonal antibodies were produced by immunizing mice with dispersed epidermal cells from a psoriatic plaque. We obtained 128 growing hybridoma clones. The immunohistochemical reactivity of the antibodies produced by these hybridomas was primarily screened on sections of skin biopsies from psoriatic plaques. Supernatants with positive staining were then tested on other dermatoses and human organs. Six supernatants stained infiltrating dermal cells and the whole epidermis in psoriatic lesions, but showed no reaction with sections from normal skin, ichthyosis, or acutely inflamed skin. With these antibodies, positive staining was also seen in some areas of the normal-appearing skin of patients with increasingly active psoriasis as well as after treatment in recently clinically healed lesions. A different and more heterogenous staining of epidermis with no or fewer infiltrating cells was seen in longstanding inflammatory disorders such as chronic eczema, neurodermatitis, lichen planus, discoid lupus erythematosus and mycosis fungoides. Scattered staining with these antibodies was in addition seen on infiltrating macrophage-like cells present also in other organs than skin and in some of the organs also other types of cells were stained, such as neck mucosal cells of the stomach, parts of duodenal mucosal cells, certain secretory cells in parotid gland, lung bronchiole and Hassall's bodies on the thymus. The cross-reactivity of antibodies to psoriatic lesions with other organs is of interest, since psoriasis might involve various tissues. Our findings support the idea that there exist unique cell surface antigens in psoriatic skin which might help elicit an immune reaction and/or be targets for such local immune reactions.

Adult↗
PubMed1988

Treatment with gamma-interferon triggers the onset of collagen arthritis in mice.

We investigated the effect of gamma-interferon (gamma-IFN) on the development of type II collagen (CII)-induced arthritis. DBA/1 mice were immunized with rat CII and 16 days later, were treated with subcutaneous injections of recombinant rat gamma-IFN into the right paws twice a week. Compared with controls, the gamma-IFN-treated mice developed arthritis with a higher frequency and severity. Immunohistochemical analysis of gamma-IFN-treated paws from CII-immunized mice revealed an increase in the numbers of class II antigen-expressing cells and an infiltration of CD4+ lymphocyte-like cells. The auto-antibody response toward CII was suppressed by gamma-IFN treatment. The findings implicate gamma-IFN in a role that triggers arthritis by enhancing local inflammatory processes in the joints, or possibly, by permitting homing of T cells to the joints.

Animals↗
PubMed1988

T-cell response to purified protein derivative after removal of Langerhans' cells from epidermal cell suspensions containing keratinocytes expressing class II transplantation antigens.

In a previous study we observed that human epidermal cell (EC) suspensions containing HLA-DR-expressing keratinocytes showed an amplified T-cell response to purified protein derivative (PPD). To evaluate further the possible immunological importance of class II transplantation antigens on keratinocytes we have compared the T-cell response to PPD in the presence of the following stimulator cells: EC suspensions from normal skin, or EC from tuberculin-reactive skin with or without removal of Langerhans' cells. The proliferation of purified T lymphocytes from peripheral blood in response to PPD in the presence of various concentrations of autologous EC was measured by [3H]thymidine incorporation on day 6. In 3 experiments out of 4 the EC from tuberculin-reactive skin, containing 28-76% HLA-DR-expressing cells as judged by immunocytochemistry (which also revealed fairly numerous HLA-DQ/-DP-expressing keratinocytes and a slight increase in CD36- and CD4- but not CD1-expressing cells), induced a more pronounced T-cell response to PPD than did normal EC. This was not the case in the fourth experiment, in which a small number of HLA-DR-(15%) and few if any HLA-DQ-/-DP-expressing keratinocytes were found. Immunomagnetic removal of CD1-reactive Langerhans' cells from the tuberculin-reactive EC suspensions resulted in a reduction of the T-cell response to PPD, in most cases down to background level (T cells alone + PPD). This study does not support the hypothesis that HLA-DR-expressing keratinocytes can in themselves act as antigen-presenting cells.

Adult↗
PubMed1988

Low dosage alpha-interferon treatment in patients with advanced cutaneous T-cell lymphoma.

Treatment with high dose (10-50 x 10(6) IU/m2 three times a week) of alpha-interferon (alpha-IFN) has been shown to induce remissions in about 50% of patients with cutaneous T-cell lymphoma. The optimal alpha-IFN dose, however, is not known. 4 patients with advanced cutaneous T-cell lymphoma were therefore treated with alpha-IFN in low doses of 2-4 x 10(6) IU/m2 three times a wk. 1 complete, 1 partial and 1 minor remission were observed. Skin biopsies before and during treatment were taken from 2 of the patients and showed improvement. Low doses of alpha-IFN can thus induce remission in patients with cutaneous T-cell lymphoma.

Adult↗
PubMed1988

Dendritic cells and macrophages expressing class II antigens in the normal rat incisor pulp.

This study has identified and characterized class II (Ia) antigen-expressing cells in the normal rat incisor pulp by immunohistochemistry and flow cytometry. Two types of Ia-expressing cells occurred: one with a pronounced dendritic appearance located primarily in the periphery of the pulp, and one with morphological characteristics similar to those of macrophages. The latter cells were mainly observed in the central portion of the pulp. A numerical ratio of 1:4 was established between the two cell types. The existence of Ia-expressing cells suggests an inherent capacity of the pulp to process and present foreign antigens.

Animals↗
PubMed1988

Enhancement of DTH reaction and inhibition of the expression of class II transplantation antigens by in vivo treatment with antibodies against gamma-interferon.

During the delayed type of hypersensitivity (DTH) reaction in the skin, class II transplantation antigens are expressed on the keratinocytes. This induction is attributed to the action of gamma-interferon (IFN-gamma). We have now studied the influence of antibodies against IFN-gamma on the DTH-reaction. Lewis rats were sensitized to 2,4-dinitro-1-fluorobenzene (DNFB) and challenged 5 days later with DNFB on the ears. Immediately before challenge each animal in one group (n = 16) was given 1 mg of mouse monoclonal antibodies (MoAb) against rats IFN-gamma, denoted DB-1, intraperitoneally (i.p.), another group (n = 15), 1 mg of an irrelevant MoAb and a third group (n = 11) was left untreated. The ear thickness was measured with a micrometer, before challenge and after 24, 48 and 72 h. At 72 h all rats were killed, the ears cut off, snap frozen and stained with immunoperoxidase using MoAbs OX 6 and OX 17, directed against rat class II antigens. The DB-1 treated group was found to have a larger ear swelling that was statistically significant at each time point compared with the other two groups. Furthermore, the animals given DB-1 showed class II antigen expression on Langerhans' cells, but almost none on keratinocytes. In contrast, the rats in the two other groups displayed a moderate to strong expression of class II antigens on keratinocytes as well as on Langerhans' cells. It is concluded that DB-1 can inhibit class II antigen expression on keratinocytes during the DTH- reaction and also enhance the local response.

Animals↗