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Biomedical subjects

U I Dahlgren

Publications and source records attributed to U I Dahlgren.

At least 19 recordsLinked to original sources
PubMed2005

Low HEMA conjugation induces high autoantibody titer in mice.

2-hydroxyethylmethacrylate (HEMA) is a known causal agent of hypersensitivity to resin composites. We have reported that immunization with HEMA conjugated to mouse serum albumin (MSA) induces an autoantibody response in mice. In this study, we investigated both the activity and the avidity of autoantibodies induced by immunization with various HEMA conjugations to MSA. Female Balb/c mice were given MSA carrying 3, 7, 15, or 22 HEMA molecules. Antigen-specific IgG and IgE antibodies were determined by ELISA, and average antibody avidity by thiocyanate dissociation. Immunization with MSA carrying the lowest number of HEMA molecules induced a significantly higher IgG and IgE anti-MSA autoantibody response, with significantly higher IgG antibody avidity, than did the more heavily conjugated preparations. The results suggest that the lower the degree of HEMA conjugation to self-protein, the higher the risk for autoantibody production to the carrier protein. These findings suggest a mechanism of potential relevance in humans.

Animals↗
PubMed2004

T-cell costimulatory capacity of oral and skin epithelial cells in vitro: presence of suppressive activity in supernatants from skin epithelial cell cultures.

Oral Langerhans cells (LC) have better T-cell costimulatory capacity than skin LC. In this study factors affecting this capacity have been assessed in a mixed epithelial cell lymphocyte reaction (MELR) assay. Flow cytometry analysis of freshly recovered cells revealed major histocompatibility complex (MHC) class II molecule expression on 7.5% of the oral epithelial cells and 9.7% of the skin epithelial cells. Monoclonal anti class II antibodies significantly reduced the T-cell proliferation in the MELR. Pretreatment of skin epithelial cells with interleukin-1beta, tumour necrosis factor-alpha or interferon (IFN)-gamma did not affect the MELR proliferation, but incubation with IFNgamma significantly suppressed the T-cell response. Transfer of supernatants from cultures of skin epithelial cells and allogeneic T cells to cultures of oral epithelial cells and T cells resulted in a reduced T-cell proliferation while supernatants from oral epithelial cells and T cells did not reduce proliferation. The higher proliferation in cultures of T cells and oral epithelial cells than in cultures containing skin epithelial cells may be due to the presence of a suppressive factor in the skin epithelial cell suspensions.

Animals↗
PubMed2004

Langerhans cells from human oral epithelium are more effective at stimulating allogeneic T cells in vitro than Langerhans cells from skin.

This report is focused on the functional capacity of Langerhans cells (LC) in the epithelium of skin and oral mucosa, which both meet different antigenic challenges. The capacity of LC from human oral and skin epithelium to provide co-stimulatory signals to T cells in vitro was compared. LC in a crude suspension of oral epithelial cells had a significantly enhanced T cell co-stimulatory capacity compared to skin epithelial cells. This applied both to cultures with concanavalin A (con-A)-stimulated syngeneic T cells and to a mixed epithelial cell lymphocyte reaction involving allogeneic T cells. The co-stimulatory capacity of oral and skin epithelial cells was reduced by >70% if monoclonal antibodies against HLA-DR, -DP and -DQ were added to the cultures with allogeneic T cells, indicating the involvement of HLA class II expressing LC. Immunohistochemistry revealed that 6% of the epithelial cells were CD1a + LC in sections from both oral and skin epithelium. Interleukin (IL)-8 production was higher in cultures of oral epithelial cells and con-A stimulated T cells than in corresponding cultures with skin epithelial cells as accessory cells. The results suggest that LC in human oral epithelium are more efficient at stimulating T cells than those of skin.

Adult↗
PubMed2003

Avidity progression of dietary antibodies in healthy and coeliac children.

In most individuals minute amounts of food proteins pass undegraded across the intestinal mucosa and trigger antibody formation. Children with coeliac disease have enhanced antibody production against gliadin as well as other dietary antigens, e.g. beta-lactoglobulin, in cow's milk. Antibody avidity, i.e. the binding strength between antibody and antigen, often increases during antibody responses and may be related to the biological effectiveness of antibodies. The aim of the present study was to determine the avidity of serum IgG antibodies against beta-lactoglobulin and gliadin in healthy children during early childhood and compare these avidities to those found in children with coeliac disease. The average antibody avidity was analysed using a thiocyanate elution assay, whereas the antibody activity of the corresponding sera was assayed by ELISA. The avidity of serum IgG antibodies against beta-lactoglobulin as well as gliadin increased with age in healthy children, even in the face of falling antibody titres to the same antigens. Children with untreated coeliac disease had IgG anti-beta-lactoglobulin antibodies of significantly higher avidity than healthy children of the same age, and the same trend was observed for IgG antigliadin antibodies. The present data suggest that the avidities of antibodies against dietary antigens increase progressively during early childhood, and that this process seems to be accelerated during active coeliac disease.

Aging↗
PubMed2002

An established immune response against ovalbumin is suppressed by a transferable serum factor produced after ovalbumin feeding: a role of CD25+ regulatory cells.

We have previously demonstrated that rats fed ovalbumin (OVA) develop a tolerogenic activity in serum, which upon transfer induces tolerance to OVA and suppression of the immune response to a bystander antigen. Here, we have extended these studies and analysed if the tolerogenic activity in serum could suppress an established immune response in the recipients. Rats were immunized with OVA, 4 and 1 week prior to the transfer of serum from either OVA-fed or control animals. Rats that received serum from OVA-fed donors had significantly lower delayed-type hypersensitivity (DTH) reaction against OVA 1 week after the serum transfer compared with the controls, and the levels of immunoglobulin (IgG) anti-OVA antibodies were significantly lower 2 and 4 weeks after serum transfer. Monomeric OVA in amounts corresponding to the OVA transferred with serum did not induce the reduction of DTH response or IgG anti-OVA antibody levels. In vitro, the proliferation of OVA-stimulated spleen cells, taken from recipients of tolerogenic serum, was significantly lower compared with spleen cells from the controls. The in vitro suppression seemed to be mediated by a population of CD25+ cells, because the removal of such cells from OVA-stimulated spleen cell suspensions resulted in increased proliferation in cultures from rats receiving tolerogenic serum. Our results showed that the tolerogenic serum factor can suppress an established immune response in recipient animals, possibly through induction of regulatory CD25+ cells. Whether this capacity might be used to influence chronic inflammatory conditions needs to be investigated.

Animals↗
PubMed2002

HEMA bound to self-protein promotes auto-antibody production in mice.

While several studies report that acrylic monomers contained in dental materials may cause hypersensitivity reactions, little is known of the associated immune response. Here we address the potential of 2-hydroxyethyl-methacrylate (HEMA) to bind to endogenous protein and elicit auto-antibody production in vivo. Albumin was incubated with HEMA at various times and pH. Following confirmation of the conjugation by inhibition of trinitrophenyl (TNP) binding, female Balb/c mice received HEMA conjugated to mouse serum albumin (MSA) in Freund's incomplete adjuvant or saline subcutaneously. ELISA was used to determine the serum antibody responses to native and modified MSA. IL-2 production in spleen cell cultures stimulated with HEMA-conjugated MSA was measured. HEMA reacted with serum albumin at physiological conditions. HEMA-conjugated MSA induced IL-2 secretion and production of IgG antibodies to native MSA. The results suggest that modification of an endogenous protein like serum albumin with HEMA may defeat the control of immune responses to this self-protein.

Animals↗
PubMed2001

IgG subclass profile of serum antigliadin antibodies and antibody-dependent cell-mediated cytotoxicity in young children with coeliac disease.

Recently, sera from children with active coeliac disease were found to efficiently induce antibody-dependent cell-mediated cytotoxicity (ADCC) of gliadin-coated cells. In the present study, the subclass profile of immunoglobulin (Ig)G antigliadin antibodies in sera from young children, with or without coeliac disease, was determined and related to the ADCC-mediating capacity of the same sera. In addition, IgG subclasses were selectively depleted from sera and the effect on ADCC-mediating was studied. Children with untreated coeliac disease had high antigliadin antibody activities of all four IgG subclasses. However, they had a particularly high proportion of IgG1 antigliadin antibodies (ratio IgG1/IgG) compared with healthy references or coeliac children in remission. In contrast, children who had high serum antigliadin antibody activity but no histological signs of enteropathy (disease references), showed significantly lower proportions of antigliadin antibodies of the IgG1 as well as the IgG3 subclass compared with healthy references or untreated coeliac children. Regression analysis showed that IgG1 and IgG3 antigliadin antibody activity correlated positively to ADCC-mediating capacity, and depletion of IgG1 from sera profoundly diminished ADCC. The results suggest that gliadin-specific antibodies of predominantly the IgG1 subclass mediate tissue-damaging immune reactions like ADCC, and may, thus, contribute to the disease process of coeliac disease.

Antibody Specificity↗
PubMed2001

Langerhans cells and T cells in oral graft versus host disease and oral lichen planus.

Chronic graft versus host disease (cGVHD) of the oral mucosa, following allogeneic stem cell transplantation, and oral lichen planus (OLP) are both mucosal diseases where the immune system is involved in the pathogenesis. Although the aetiology of the two conditions is different, they present with a similar clinical appearance. This study compares the two diseases regarding the distribution of cells, which are expressing cell surface markers of interest for inflammatory responses. Monoclonal antibodies (MoAbs) were used in standard immunohistochemical procedures. CD1a+, CD80+ and CD86+ cells in the epithelium of OLP- and cGVHD lesions had the dendritic morphology of Langerhans cells (LC). Higher frequencies of CD1a+ LC as well as CD25+ cells were observed in the OLP epithelium than in the cGVHD epithelium. The OLP lesions showed higher frequencies of subepithelial cells expressing CD1a, CD86, CD4, CD8 and CD25 than the cGVHD lesions. Notably there was a significantly higher frequency of CD25+ cells in the epithelium and the connective tissue of OLP than in cGVHD. These cells might represent regulatory T cells. In conclusion, cGVHD and OLP show marked differences at the cellular level despite similar clinical appearance. Hence, the findings indicate differences in the regulation of the inflammatory response between the two conditions.

Adult↗
PubMed2000

Human and rat mononuclear cell proliferation show different sensitivity, in vitro, to single constituents of dental composite resins.

The aim of this study was to evaluate the effect of 11 constituents of dental composite resins on ConA-induced proliferation of rat mononuclear cells. We also wanted to compare the sensitivity of rat and human mononuclear cells, to find out if results from a rat cell assay could be extrapolated to human conditions. The variable used for this purpose was the dose at 50% inhibition of proliferation (ID(50)). Mononuclear cells derived from rat spleens and human venous blood were used. The effects of the substances on rat and human cell proliferation were evaluated with and without stimulation by Concanavalin A. The ID(50) rank order of the tested substance categories was similar for both species, i.e., the monomers inhibited at the lowest concentration, the stabilizer at intermediate, and the initiators at the highest concentrations. In spite of a similar inhibition rank order, there were significant differences in sensitivity to the substances between the species. In conclusion, the results from this study together with the fact that the substances are handled by and used in humans, would favor the use of human cells when studying the effect of constituents of dental composite resins in vitro.

Animals↗
PubMed2000

Tolerance and bystander suppression, with involvement of CD25-positive cells, is induced in rats receiving serum from ovalbumin-fed donors.

In the present study we have investigated if transfer of serum from rats fed ovalbumin (OVA) leads to specific tolerance and bystander suppression in recipient animals. Rats that received serum from OVA-fed donors had a lower delayed-type hypersensitivity reaction (DTH) both against OVA and the bystander antigen, human serum albumin (HSA), compared with recipients given serum from control-fed animals. The in vitro proliferation of OVA- and HSA-stimulated spleen cells and the serum immunoglobulin G (IgG) antibody levels against OVA and HSA were also lower in the animals that received serum from OVA-fed animals compared with the controls. There was no reduction of the immune response to HSA if the recipient animals, given serum from OVA-fed donors were immunized with OVA and HSA at separate sites. Depletion of CD25-positive cells from spleen suspensions from rats receiving serum from OVA-fed animals, resulted in a significant increase in proliferation of OVA-stimulated cells in vitro compared with the controls. Tolerogenic activity could be demonstrated, both in a fraction from serum containing structures smaller than 100 000 MW and a fraction with components larger than 100 000 MW, compared with size-related serum fractions obtained from control-fed animals. This implies that the tolerogenic activity could be mediated by more than one serum component. The tolerogenic activity was most prominent in animals receiving the larger size fraction with a more pronounced suppression of the DTH reaction and lower levels of IgG anti-OVA antibodies in serum compared with controls. A novel finding in the present study was that the transfer of serum, collected from rats fed OVA, led to a reduction of the immune response to a bystander antigen in the recipients. This suggests that the induced tolerance is at least partly due to suppression. The suppression could have been mediated by CD25-positive cells since removal of these cells resulted in an increased in vitro proliferation against OVA.

Animals↗
PubMed1999

Neonatal colonization of rats induces immunological tolerance to bacterial antigens.

We wanted to investigate the immunological events occurring in rats intestinally colonized from birth (neonatally) or at adult age with an ovalbumin (OVA)-producing Escherichia coli O6K13 strain, carrying type 1 pili. The neonatally colonized animals responded with lower delayed type hypersensitivity (DTH) against OVA and lower levels of IgG antibodies against OVA, O6 lipopolysaccharide (LPS) and type 1 pili compared to age-matched controls. The IgG antibody response against the bystander antigen, human serum albumin (HSA), was lower in the neonatally colonized animals than in the controls co-immunized with HSA and E. coli, indicating a release of suppressive factors induced by the bacterial antigens. The adult colonized animals showed an increased DTH and antibody response against OVA after immunization. They also had high pre-immunization levels of IgG anti-O6 LPS antibodies compared to controls. However, the relative increase in IgG anti-O6 LPS antibody levels after the immunization with dead E. coli was much lower in the adult colonized animals. The present results suggest that neonatal animals develop tolerance against antigen on bacterial colonizers of the intestine. In addition, this tolerance contains components of suppression.

Animals↗
PubMed1999

Distribution of interleukin-2, -4, -10, tumour necrosis factor-alpha and transforming growth factor-beta mRNAs in oral lichen planus.

In the present study, MRNA for the cytokines interleukin-2 (IL-2), IL-4, IL-10 tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor beta-1 (TGF-beta-1) were investigated in oral lichen planus (OLP) lesions using in situ hybridization with 35S-labelled oligonucleotide probes on frozen tissue sections. In addition, the expression of interferon-gamma (IFN-gamma), IL-10 and IL-4 mRNAs was analysed in cultured lesional T lymphocytes from oral lichen planus by polymerase chain reaction. Cells expressing mRNA for IL-2, IL-4, IL-10, TNF-alpha and TGF-beta 1 were found in all the biopsies studied. Approximately 1-2% of the total number of infiltrating cells in the lesions were positive for each of the different cytokine mRNAs. Most biopsies contained basement membrane-oriented, mRNA-positive cells. In the cultured T-cell lines, message for IFN-gamma was detected in all the patients, IL-10 in all but one, and IL-4 in just one of the seven patients investigated. The results suggest that mRNA for both pro- and anti-inflammatory cytokines, i.e., mixed T-helper 1 (TH1) and TH2 cytokine profiles, are generated simultaneously by a limited number of cells in chronic lesions of OLP.

Adult↗
PubMed1999

Active suppression in orally tolerized rats coincides with in situ transforming growth factor-beta (TGF-beta) expression in the draining lymph nodes.

Adult rats were fed pellets containing ovalbumin (OvA) during 4 weeks, and were 2 weeks thereafter immunized subcutaneously with a mixture of OvA and human serum albumin (HSA) in Freund's complete adjuvant (day 0). As a result of the immunization, the draining lymph nodes of the nontolerized (control) rats were heavily enlarged from day 10 to day 18; however, this size increase was absent in the OvA-fed rats. This manifestation of active suppression in the tolerized rats was preceded by the appearance of scattered CD4+ TGF-beta-expressing T cells in the T cell area of their lymph nodes (days 5-8); correspondingly, the levels of TGF-beta mRNA in the nodes were elevated in the tolerant rats compared with the control rats. The anti-OvA antibody levels in sera from the rats revealed that there was an initial B cell priming in the OvA-fed group, with levels higher than in the control group during the first week. Thereafter, suppression governed the response, and from day 10 onwards the anti-OvA levels were considerably lower than in the controls. When other groups of animals were pretreated with neutralizing anti-TGF-beta antibodies 1 day before the immunization, the anti-OvA response of the OvA-fed rats was restored to the levels of the control group, demonstrating the importance of TGF-beta in the maintenance of suppression. In conclusion, we demonstrate that TGF-beta-producing cells appear in the draining lymph nodes shortly after immunization in rats made orally tolerant using a relatively high-dose feeding regime; these cells are probably responsible for the down-regulation of the immune response observed in the OvA-fed rats.

Administration, Oral↗
PubMed1999

Antibodies given orally in the neonatal period can affect the immune response for two generations: evidence for active maternal influence on the newborn's immune system.

Two day old Wistar rats were tube fed with 1 or 10 micrograms of a mouse IgG1 monoclonal anti-idiotypic (a-Id) antibody that was directed against an anti-Escherichia coli-K13 capsular polysaccharide antibody. A control group was given 10 micrograms of an unrelated control antibody. Six weeks after the administration of antibodies, the rats were intestinally colonised with an ovalbumin (OVA)-producing E. coli O6K13 strain. At 8 weeks of age, the male rats (first generation) and the offsprings of the female rats (second generation), were parenterally immunised with OVA and dead wild type E. coli O6K13, and the immune response was followed. In the rats of the first generation, there were no major differences between the groups in the immune response to the bacterium. However, the offspring of the neonatally a-Id administered rats had a profoundly affected immune response to the idiotypically connected antigen K13, but also to other antigens on the bacteria. Thus, a-Id treatment in the first generation gave, in the second generation, a greatly enhanced serum antibody response to the spatially related antigens OVA and O6 LPS, as well as to the idiotypically connected antigen K13. Concurrently, the in vitro spleen cell proliferative response to both OVA and the wild type bacterium was lowered. Overall, greater effects were seen with the higher dose of a-Id. In conclusion, our results demonstrate that by giving monoclonal antibodies idiotypically connected to a single bacterial component to neonatal rats, one profoundly influence the immune response also to other-spatially related-bacterial antigens in their offsprings.

Administration, Oral↗
PubMed1999

Langerhans cells from oral epithelium are more effective in stimulating allogeneic t-cells in vitro than Langerhans cells from skin epithelium.

Dendritic cells, such as Langerhans cells (LC), in different ectodermal compartments may have different functional capabilities. The present study was undertaken to compare oral Langerhans cells (LC) with those of the epidermis in terms of their ability to co-stimulate T-cells in vitro. A Mixed Epithelial Cell Lymphocyte Reaction (MELR) and a mitogen-driven (concanavalin A) T-cell proliferation assay were used. In both assays, LC in a crude cell suspension of freshly isolated oral epithelial cells were found to be five times more effective in mediating T-cell proliferation than freshly isolated epidermal LC. Twenty-four-hour cell culture at 37 degrees C enhanced the T-cell response in the MELR compared with cells cultured at 4 degrees C. This applied to both skin and oral epithelial cells. Oral and skin epithelial cell suspensions depleted of LC lost the capacity to stimulate allogeneic T-cells. Incubation of the epithelial cell suspensions with recombinant Granulocyte/Macrophage-Colony Stimulating Factor (rGM-CSF) did not enhance the co-stimulating capacity of the LC. Titration of different numbers of oral and skin LC to T-cells showed that skin LC were never able to reach more than 44% of the maximal stimulatory capacity of oral LC. Data show that oral LC are more efficient than skin LC in providing co-stimulatory signals to T-cells, suggesting a difference in functional capacity between the two cell populations.

Animals↗
PubMed1999

Reduced in vivo cell-mediated immune responses to mumps, tuberculin, and streptokinase/streptodornase but not to Candida albicans in oral lichen planus.

Oral lichen planus is considered to be a T-cell-mediated disease. The purpose of this study was to investigate the capacity of T-lymphocytes in oral lichen planus patients to respond to a number of commonly encountered environmental antigens in vivo. To do this, we assessed dermal delayed-type hypersensitivity responses to mumps, streptokinase/streptodornase, Candida albicans, and purified protein derivative of tuberculin (PPD) in 17 oral lichen planus patients and in matched controls. Reduced induration in response toward mumps, PPD, and streptokinase/streptodornase was demonstrated in oral lichen planus patients compared with controls. In addition, the total sum of induration diameters was decreased in the patients. However, C. albicans stimulation resulted in similar levels of response in both groups. The differences in induration size between matched patients and controls for mumps and PPD were thus significantly greater than the corresponding differences for the C. albicans antigen. This suggests that a selective difference in the response to these antigens exists in oral lichen planus patients. The results may point to a loss of memory T-helper function to infrequently encountered environmental antigens, represented by mumps, PPD, and streptokinase/streptodornase, contrarily to memory function to common antigens (C. albicans), which seem to be unaffected.

Aged↗