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Biomedical subjects

E Telemo

Publications and source records attributed to E Telemo.

At least 19 recordsLinked to original sources
PubMed2005

A full flora, but not monocolonization by Escherichia coli or lactobacilli, supports tolerogenic processing of a fed antigen.

Fed protein undergoes processing and coupling to major histocompatibility complex (MHC) II molecules during passage through the intestinal epithelium, generating a tolerogenic form of the antigen in serum. Transfer of this factor to naïve animals induces tolerance in the recipient. In this study, we investigate what impact colonization with Gram-positive (Lactobacillus plantarum) or Gram-negative (Escherichia coli) bacteria has on tolerogenic processing in the gut. Germ-free (GF), monocolonized or conventional mice were fed ovalbumin (OVA), and their serum was collected and transferred to naïve conventional recipients that were tested for delayed-type hypersensitivity against OVA after parenteral immunization. A transferable tolerogenic factor was produced by conventional mice, but not by mice that were germ free or monocolonized with either E. coli or L. plantarum. Conventional, but neither GF nor monocolonized mice showed upregulation of MHCII expression in the epithelium of small intestine. The results suggest that a complex intestinal microflora is needed to support oral tolerance development.

Administration, Oral↗
PubMed2004

The ratio of n-6 to n-3 fatty acids in maternal diet influences the induction of neonatal immunological tolerance to ovalbumin.

Prevalence of allergy is increasing in many countries and might be related to changed environmental factors, such as dietary fatty acids (FA). The present study investigates whether dietary ratio of n-6 to n-3 FA influences the induction of immunological tolerance to ovalbumin (OA) in neonatal rats. During late gestation and throughout lactation Sprague-Dawley rats were fed a diet containing 7% linseed oil (n-3 diet), sunflower oil (n-6 diet) or soybean oil (n-6/n-3 diet). At 10-16 days of age the rat offspring were subsequently exposed, or not, to OA via the milk. The offspring were weaned onto the same diets as the mothers and immunized with OA and the bystander antigen human serum albumin (HSA). In the offspring on the n-3 diet exposure to OA via the milk resulted in lower delayed type hypersensitivity reaction (DTH) and antibody responses against both OA and HSA, compared to those in the offspring not exposed to OA, indicating the induction of oral tolerance. In the offspring on the n-6 diet, the exposure to OA led to depressed specific immune responses against only OA, not HSA. In the offspring on the n-6/n-3 diet oral exposure to OA did not influence immune responses against OA, or HSA. The results indicate that the dietary ratio of n-6/n-3 FA is important for the induction of neonatal oral tolerance. Thus nonoptimal feeding may have effects on the development of immunological tolerance to dietary antigen ingested by the mother. The ratio of n-6/n-3 FA in the diet may be considered in the context of increased prevalence of allergy.

Animals↗
PubMed2003

A kinetic study in adults with food hypersensitivity assessed as eosinophil activation in fecal samples.

BACKGROUND: Immune-mediated food hypersensitivity affecting the gut is difficult to evaluate, and objective tools to diagnose local gastrointestinal (GI) inflammatory reactions are lacking. OBJECTIVES: To determine whether allergic manifestations in adults with a history of food-related GI symptoms could be assessed in feces during symptomatic and non-symptomatic periods, using the surrogate markers, eosinophil cationic protein (ECP), eosinophil protein X (EPX) and myeloperoxidase (MPO). METHODS: Thirteen subjects with food hypersensitivity-related GI symptoms, confirmed by a positive double-blind placebo-controlled food challenge (DBPCFC), were subjected to an open kinetic food challenge design for 6 weeks. Symptoms were recorded and scored during the 3-week study period and stool samples were obtained every day. The surrogate markers ECP, EPX and MPO were measured in the supernatants from feces samples. RESULTS: A significant increase in abdominal pain, distension and flatulence was observed during challenge, with a gradual decrease during elimination diet. Both between days and subjects, EPX levels were more frequently increased compared to ECP and MPO. Individuals with a history of a short duration of symptoms had significantly higher mean levels of EPX and MPO than those with a longer duration of symptoms. CONCLUSIONS: An overall increase in levels of eosinophil markers, in particular EPX, was observed in feces from patients with food-related GI symptoms. However, rather than being a tool to differentiate symptomatic from non-symptomatic periods, EPX might be used for detecting an ongoing clinical or subclinical chronic inflammation, that may have an impact on the patient's clinical course of GI symptoms.

Adult↗
PubMed2002

Loss of ileal IgA+ plasma cells and of CD4+ lymphocytes in ileal Peyer's patches of vitamin A deficient rats.

Child mortality in diarrhoeal disease is increased significantly by vitamin A deficiency in poor countries. The pathological mechanisms are not known in detail. However, in this paper we report that vitamin A-deficient Wistar rats had much reduced IgA+ plasma cells in the ileal lamina propria (eightfold reduction from 470 cells/mm(2), P = 0.009), as well as a prominent reduction of CD4+ cells in the parafollicular regions of ileal Peyer's patches (reduction from 7200 to 105 cells/mm(2), P = 0.009). IL-2Ralpha-chain (CD25) positive lymphocytes in the ileal Peyer's patches were also reduced significantly in vitamin A deficiency (from 1400 to 300 cells/mm(2), P = 0.009). The density of CD8 cells tended to be increased relative to the control animals (from 5100 to 6000 cells/mm(2), not statistically significant). In conclusion, the marked decrease of lamina propria IgA+ plasma cells may be one cause of the high diarrhoeal mortality in vitamin A deficiency. This, in turn, appears to be related to reduced numbers of activated or regulatory CD4+ T cells in Peyer's patches.

Animals↗
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↗
PubMed2001

"Tolerosomes" are produced by intestinal epithelial cells.

The development of immunological tolerance to orally fed antigens depends on the sampling, processing and transportation events followed in the intestinal epithelium. We present here a description of a "tolerosome": a supra-molecular, exosome-like structure assembled in and released from the small intestinal epithelial cell. The tolerosome is a approximately 40 nm large vesicular structure that carries MHC class II (MHC II) with bound antigenic peptides sampled from the gut lumen. Tolerosomes isolated from serum shortly after antigen feeding or from an in vitro pulsed intestinal epithelial cell line are fully capable of inducing antigen specific tolerance in naive recipient animals. Purified tolerosomes represent a structure by which fed antigens can be efficiently presented to the immune system. Removal of the tolerosomes from serum by ultracentrifugation or absorption of MHC II results in abrogated tolerance development.

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↗
PubMed2000

Expression of CD1d in the duodenum of patients with cow's milk hypersensitivity.

CD1 cell surface glycoproteins represent a family of non-major histocompatibility complex (MHC) encoded antigen-presenting molecules. All members of the CD1 family appear to mediate the recognition of microbial or endogenous lipid and glycolipid antigens. The recognition of CD1d by a unique subset of natural killer (NK) T cells that leads to rapid production of large amounts of both type 1 and type 2 cytokines can be augmented by some synthetic glycolipids. Because of the proposed role of such CD1d-restricted T cells in immunoregulation, we hypothesized that CD1d molecules participate in mucosal immune responses in patients with gastrointestinal symptoms owing to food hypersensitivity. Patients of that category represent a heterogeneous group in which poorly defined immunological mechanisms are believed to contribute to disease pathogenesis. The expression of CD1 in duodenal biopsy samples from six patients with verified intolerance to cow's milk and six healthy controls was studied by immunoperoxidase staining of cryostat sections using a panel of mouse monoclonal antibodies (MoAbs) specific for CD1a, b, c, and d. Large numbers of CD1d positive cells were found in the lamina propria of all the patients, both during the symptomatic and the asymptomatic periods, whereas healthy controls were virtually devoid of CD1d expression in the duodenum. The localization of CD1d positive cells corresponded to areas where B cells, plasma cells and dendritic cells (DC) were present. A positive correlation was found between the numbers of CD1d(+) and CD19(+) cells in the lamina propria. In contrast to previous reports, no CD1d expression was found on the epithelial cells. Although less numerous than CD1d(+) the CD1c(+) cells were also present in all the patients and in five out of six controls. No staining for CD1a or CD1b was detected in the duodenal biopsy samples from any of the subjects. The exclusive presence of CD1d in the duodenal lamina propria of the patients with cow's milk hypersensitivity might suggest the participation of these molecules in the pathogenesis of allergic reactions to food.

Adult↗
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

An IL-2-toxin, DAB389IL-2, inhibits delayed-type hypersensitivity but enhances IgE antibody production.

BACKGROUND: Expression of high-affinity IL-2 receptor (IL-2R) on T lymphocytes, key cells in chronic inflammation, is a T-cell activation marker. OBJECTIVE: We sought to evaluate the effect of the fusion protein DAB389IL-2, which kills cells bearing IL-2R, on delayed-type hypersensitivity and antibody production in Brown Norway rats sensitized with trimellitic anhydride (TMA). METHODS: DAB389IL-2 (25 micrograms/kg/day) or placebo was administered intraperitoneally for 8 days over the period of sensitization, starting 2 days before sensitization. RESULTS: The administration of DAB389IL-2 resulted in a one-third reduction in the number of IL-2R-bearing cells and significant weight loss of animals. Delayed-type hypersensitivity, evaluated at 5 weeks after sensitization, was significantly inhibited by treatment with DAB389IL-2. In contrast, production of IgE anti-TMA antibodies after sensitization was increased by treatment with DAB389IL-2. DAB389IL-2 affected neither IgG anti-TMA antibody nor total IgE levels. CONCLUSION: These data imply that systemic administration of DAB389IL-2 in Brown Norway rats influences cells that have regulatory effects on the immune system, resulting in a switch from a TH1 to a TH2 type of immune response.

Allergens↗
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

Immunomodulatory effects of Lactobacillus plantarum colonizing the intestine of gnotobiotic rats.

We have studied the effect of the probiotic strain Lactobacillus plantarum 299v on the immune functions of gnotobiotic rats. One group of germ-free rats was colonized with the type 1-fimbriated Escherichia coli O6:K13:H1 and another group with the same E. coli strain together with L. plantarum 299v. One and 5 weeks after colonization, bacterial numbers were determined in the contents of the small intestine, caecum and mesenteric lymph nodes. Small intestinal sections were examined for CD8+, CD4+, CD25+ (IL-2R alpha-chain), IgA+ and MHC class II+ cells and mitogen-induced spleen cell proliferation was determined. Immunoglobulin levels and E. coli-specific antibodies were measured in serum. Rats given L. plantarum in addition to E. coli showed lower counts of E. coli in the small intestine and caecum 1 week after colonization compared with the group colonized with E. coli alone, but similar levels after 5 weeks. Rats colonized with L. plantarum + E. coli had significantly higher total serum IgA levels and marginally higher IgM and IgA antibody levels against E. coli than those colonized with E. coli alone. They also showed a significantly increased density of CD25+ cells in the lamina propria and displayed a decreased proliferative spleen cell response after stimulation with concanavalin A or E. coli 1 week after colonization. The results indicate that L. plantarum colonization competes with E. coli for intestinal colonization and can influence intestinal and systemic immunity.

Animals↗
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↗
PubMed1998

Bystander suppression of occupational hapten sensitization in rats made tolerant to ovalbumin.

Feeding a soluble antigen to an animal is known to cause a state of unresponsiveness against this antigen. If this antigen is given together with another antigen during the sensitization procedure, impairment of the response to the new antigen can also be seen, a phenomenon referred to as bystander suppression. The induction of tolerance against ovalbumin (OvA) and the effect of bystander suppression on the response to the hapten trimellitic anhydride (TMA), a cause of occupational asthma, were studied in Brown-Norway rats. Rats were fed either OvA-containing pellets or standard diet for 16 days before sensitization with the mixture of TMA and OvA. The animals were followed for 6 weeks after sensitization. Animals made tolerant to OvA showed a significantly suppressed delayed-type hypersensitivity (DTH) reaction against both OvA and TMA compared with the nontolerized control group at 5 weeks after sensitization, implying bystander suppression. By contrast, immunoglobulin (Ig)E and IgG antibody levels were suppressed only against OvA, whereas anti-TMA antibody levels were not affected. Airway eosinophilia after a single aerosol challenge at 6 weeks after sensitization using TMA conjugated to rat serum albumin, correlated with IgE anti-TMA levels in the group made tolerant to OvA and was not affected by OvA ingestion. In conclusion, suppressive factors released in ovalbumin-tolerant rats when they are challenged with ovalbumin, can suppress the response to trimellitic anhydride and this suppression is more pronounced for T-helper1-type responses.

Airway Resistance↗