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Esbjörn Telemo

Publications and source records attributed to Esbjörn Telemo.

15 recordsLinked to original sources
PubMed2006

MHC expression and chemokine production in the murine vagina following intra-vaginal administration of ligands to toll-like receptors 3, 7 and 9.

The expression of MHC class I, MHC class II and the chemokines IP-10, MIP-1alpha, RANTES, fractalkine and I-TAC has been analyzed after intra-vaginal treatment with three synthetic toll-like receptors (TLR) agonists-double-stranded RNA (poly I:C), imiquimod and CpG-rich oligonucleotides (CpG-ODN). These compounds act mainly through TLR3, TLR7 and TLR9, respectively. CpG-ODN induced an accumulation of leucocytes in the vagina, and a strong up-regulation of MHC class I expression on both leucocytes and epithelial cells. Imiquimod and poly I:C induced a weak MHC class I up-regulation in the epithelium but not in the lamina propria. Neither treatment had any profound effect on expression of MHC class II on epithelial cells but poly I:C and to a lesser extent CpG-ODN, up-regulated MHC class II staining intensity which, in the case of CpG-ODN, treatment, was associated with a strong accumulation of CD11c-positive dendritic cells. All three treatments induced an early (8h) but transient IP-10 response. Imiquimod and CpG-ODN, but not poly I:C induced an early MIP-1alpha response which remained for at least 7 days in CpG-ODN-treated animals but not in imiquimod-treated mice. Poly I:C and CpG-ODN, but not imiquimod, induced significant levels of RANTES at different time-points post-treatment. None of the treatments induced any significant changes in the levels of fractalkine, I-TAC or IFN-alpha. These studies have implications for the manipulation of the genital immune response and also improving the outcome of vaginal immunotherapy.

Adjuvants, Immunologic↗
PubMed2006

Impaired regulatory T cell function in germ-free mice.

Regulatory T cells (Treg) are crucial for the maintenance of tolerance to auto-antigens and harmless exogenous antigens. Here, we studied the role of the commensal microbiota for the development and function of Treg. CD4+CD25+ T cells were obtained from peripheral lymph nodes (PLN) and mesenteric lymph nodes (MLN) of germ-free (GF) and conventional (conv) NMRI mice and tested for phenotype and functional suppressive capacity. CD4+CD25+ T cells from GF mice showed a lower relative gene expression of fork head box p3 gene (Foxp3) and were not as potent suppressors in vitro as CD4+CD25+ T cells from conv animals. Intracellular staining for Foxp3 and CTLA-4 revealed proportional and regional differences in putative Treg subsets between conv and GF mice. Fewer of the CD4+CD25+ T cells in GF MLN expressed Foxp3 and CTLA-4, while the expression of these markers was similar amongst the CD4+CD25+ T cells in PLN of conv and GF mice. The largest difference between conv and GF Treg was observed in the liver draining celiac lymph node, where GF mice had fewer putative Treg as compared to conv mice. We propose that the presence of a microbial flora favors the development of a fully functional Treg population.

Animals↗
PubMed2006

Oral tolerance induction by mucosal administration of cholera toxin B-coupled antigen involves T-cell proliferation in vivo and is not affected by depletion of CD25+ T cells.

Oral administration of antigens coupled to the B subunit of the cholera toxin (CTB) can dramatically reduce the amount of antigen needed for tolerance induction and has been used in several animal models to suppress conditions where the immune system overreacts to foreign and self-antigens. In this study, the cellular events following oral administration of CTB-coupled antigen was investigated. As a model system, limited numbers of CSFE-labelled cells from influenza haemagglutinin peptide (HApep) T-cell transgenic mice were transferred to wild type mice and the mice were then given CTB-coupled HApep orally. The inductive events of CTB-induced tolerance was characterized by extensive proliferation of HApep-specific T cells in the mesenteric lymph nodes (MLNs) and in the spleen. The proliferating cells up-regulated the gut homing molecule alpha4beta7 and down-regulated the high endothelial venule binding molecule L-selectin. Addition of the whole cholera toxin (CT) to CTB-HApep showed a similar pattern as CTB-HApep feeding, with antigen-specific proliferation in the MLN and spleen and expression of alpha4beta7 on the proliferating cells. However, addition of CT to CTB-HApep, produced a stronger and faster proliferative response and abrogated CTB-HA mediated oral tolerance. Feeding of CTB-HApep expanded CD25+ cells in the MLNs. CTB-induced oral tolerance could, however, not be explained by CD25+ dependent regulatory activity, as oral administration of CTB-HApep to mice depleted of CD25+ cells still gave rise to systemic tolerance. Thus, several mechanisms might co-orchestrate the systemic tolerance seen in response to feeding with CTB-coupled antigen.

Administration, Oral↗
PubMed2005

Modification of IgE binding to beta-lactoglobulin by fermentation and proteolysis of cow's milk.

The effect of fermentation by Lactobacilli and of proteolytic hydrolysis of whole milk on the IgE binding ability of beta-lactoglobulin was studied using an ELISA inhibition assay. Sera from nine adult milk allergic patients were tested. The individual sera showed a similar inhibition pattern in the changes during fermentation and proteolysis. The degradation of beta-lactoglobulin was studied with liquid chromatography. In general, fermentation with Lactobacilli gave little effect on IgE binding, even though chromatography data showed a gradual degradation of beta-lactoglobulin. Proteolysis with trypsin, however, gave extensive degradation of beta-lactoglobulin and strongly decreased IgE binding. In addition, we measured the inhibition pattern of beta-lactoglobulin in various selected commercially available fermented milk products. These showed an IgE binding capacity similar to that of nonfermented high pasteurized milk.

Adult↗
PubMed2005

Induction of antigen-specific regulatory T cells in the liver-draining celiac lymph node following oral antigen administration.

Regulatory T cells are induced by oral administration of an antigen, but the physiological requirements and localization of the inductive sites are largely unknown. Using an adoptive transfer system of cells transgenic for ovalbumin T-cell receptor (OVA TCR tg), we found that antigen-specific CD4+ T cells were activated in the liver-draining celiac lymph node (CLN) shortly after ovalbumin feeding, and that a significantly higher proportion of the T cells in the CLN developed into the putative regulatory phenotype [co-expressing CD25 with the glucocortico-induced tumour necrosis factor (TNF) receptor family related gene (GITR), cytotoxic T-lymphocyte antigen (CTLA)-4 and CD103] than in Peyer's patches, the mesenteric and peripheral lymph nodes and the spleen. In addition, a particularly high level of expression of CD103 on the OVA-specific T cells in the CLN may favour homing to the epithelium of the intestine. While equally suppressive, OVA tg T cells isolated from the CLN of OVA-fed DO11.10 mice were less dependent on transforming growth factor (TGF)-beta for suppression than cells isolated from the peripheral and mesenteric lymph nodes, which indicates the involvement of an additional suppressive mechanism. The expression of FoxP3 was not up-regulated in any of the lymph node compartments studied. Our phenotypic and functional findings suggest that the induction of regulatory T cells in the CLN may be relevant in the control of the immune response to dietary antigens.

Administration, Oral↗
PubMed2005

Tolerosome-induced oral tolerance is MHC dependent.

Oral administration of a protein antigen generates a serum factor that induces tolerance when transferred into naïve recipients. This serum factor has been described in rats as consisting of exosome-like structures or tolerosomes, which express major histocompatibility complex class II molecules (MHCII) and mediate antigen-specific tolerance. In this study, we investigated the functions of serum-derived tolerosomes both in vivo and in vitro. Tolerosomes were purified from the 100,000 g pellet fraction of serum from ovalbumin (OVA)-fed mice. When transferred into naïve recipient mice, the tolerosomes mediated OVA-specific tolerance. We also found that tolerosomes from OVA-fed mice induced the activation of OVA-specific T cells both in vivo and in vitro. The inoculation of severe combined immunodeficiency (SCID) mice with an interferon-gamma-producing cell line normalized the expression of MHCII in the intestinal epithelial cells and restored their ability to generate tolerosomes. Syngeneic but not allogeneic transfer of tolerosomes from OVA-fed donors induced tolerance in the recipients. Our results show that tolerosomes can be isolated from mouse serum, that tolerosome-induced oral tolerance requires MHCII expression in intestinal epithelial cells, and that tolerosomes are functional only in syngeneic recipients.

Administration, Oral↗
PubMed2004

Modulation of neonatal immunological tolerance to ovalbumin by maternal essential fatty acid intake.

The present study examines whether dietary essential fatty acid (EFA) intake influences the induction of oral tolerance to ovalbumin (OA) in neonatal and adult rats. During late gestation and throughout lactation Sprague-Dawley rats were fed a diet supplemented (S) with EFA (7% soybean oil), or a diet deficient (D) in EFA (7% hydrogenated lard). The rat offspring were subsequently exposed to OA either via the milk at 10-16 days (neonatal rats), or as adults via the drinking water at 7-9 wk of age. Oral administration of OA to the adult rats lead to suppression of the delayed-type hypersensitivity (DTH) reactivity and IgG antibody response against OA, which was not influenced by their diets. In the offspring of the dams fed the D diet antigen exposure via the milk resulted in suppression of the serum antibody levels and DTH reaction against OA indicating induction of oral tolerance. Higher transforming growth factor beta (TGF-beta) mRNA levels in the draining lymph nodes suggested this to be mediated by regulatory T cells. In contrast, OA exposure of the dams fed the S diet did not result in a suppressed OA response of their offspring. Thus, the quality of FA ingested by the mother may have effects on the development of immunological tolerance to dietary antigens in the offspring. Our results might have importance for the understanding of the increase in allergy related to the Western type of diet.

Age Factors↗
PubMed2003

Antigen presentation and processing in the intestinal mucosa and lymphocyte homing.

OBJECTIVE: The mucosal surface of the gastro-intestinal tract is our major interface to the environment. Much of the control of the immune response to the myriads of antigen present at this interface is mediated by professional antigen-presenting dendritic cells (DCs). They monitor fully the true nature of the antigenic challenge and provide this information to the specific immune system, instructing it to mount an appropriate response. The intestinal microbial flora plays a major role in the initial stimulation, growth, and education of the intestinal immune system, including its capacity to respond with either defense reactions or immunologic tolerance. DATA SOURCES: To review the recent literature on the process of antigen sampling, processing, presentation, and initiation of immune recognition that take place on mucosal surfaces and their draining lymph nodes, especially the intestinal mucosa. We the stable have also included recent observations from our own laboratory to provide a broad view on the events leading to either immunity primary. or tolerance to environmental antigens. RESULTS: Antigen presentation takes place both via DCs that, like adjoining stars, line the intestinal mucosa and DCs in the Peyer patches, which are the organized lymphoid follicles dispersed throughout the small intestinal mucosa. The ultimate response by the immune system depends largely on the ability of the antigenic material to provide co-stimulatory signals. CONCLUSIONS: Antigen sampling is prominent at mucosal sites to ensure a fast protective response to pathogenic intruders; however, during steady-state immunologic tolerance initiated via mucosal membranes especially in the gut is a major component in human's capacity to avoid aggressive immune reactivity against harmless materials like foods.

Animals↗
PubMed2003

Breast-feeding, infant formulas, and the immune system.

OBJECTIVE: Breast-feeding provides many advantages to the offspring, but presently there is an ongoing debate whether or not it prevents allergy any better than certain formulas. This report reviews the mechanisms involved and discusses how breast-feeding may protect against allergy. DATA SOURCES: The review builds on an internet-based literature search in addition to our own data. RESULTS: Human milk is the food best adapted to the needs of the offspring, also because it provides efficient protection against infections and actively stimulates the development of the infant's own immune system. The major host defense system is provided via the secretory IgA antibodies produced in the mammary glands by lymphocytes, which have migrated there from the mother's gut mucosa. Therefore, these antibodies in the milk are primarily directed against the microbes in the mother's gut and her food proteins. As a result, breast-feeding starting directly after delivery will provide an excellent defense against the microbes normally meeting the neonate and needed to induce development of its immune system. The milk also contains numerous components, which seem to enhance the infant's host defense as well as capacity to develop tolerance, helping to avoiding allergic reactivity to foods, etc. CONCLUSIONS: Several studies show that breast-feeding prevents allergic diseases, but there are also good disagreeing studies. Supported by animal data, it seems that protection is enhanced in areas with more advantageous fat intake, inter alia lower ratio of n-6/n-3 fatty acids. Breast-feeding seems to protect against future development of allergic diseases, but possibly less so in countries with an untoward maternal fat intake.

Animals↗
PubMed2003

Seasonal intestinal inflammation in patients with birch pollen allergy.

BACKGROUND: The pathophysiologic interactions of inflammatory reactions between the mucosa of the respiratory tract and that of the gastrointestinal tract in individuals with allergy are poorly studied, despite the fact that allergic symptoms in the airways and the gastrointestinal tract might arise in the same patient. OBJECTIVE: The objective of this study was to examine the inflammatory response histologically by enumerating eosinophils, IgE+ cells, and T cells in duodenal biopsy specimens in adult patients with IgE-mediated birch pollen allergy during the birch pollen season and off-season. METHODS: Nine patients with birch pollen allergy verified by skin prick test and serum IgE antibodies were investigated toward the end of the birch pollen season and again 6 months later (off-season). Duodenal biopsy specimens were obtained and studied by immunostaining for the eosinophil major basic protein (MBP), IgE, and CD3+ T cells. RESULTS: Oral allergy syndrome to birch-associated foods was present in all patients as indicated by questionnaire. Duodenal increases of MBP+ eosinophils and IgE-bearing cells were found in the patients during the birch pollen season as compared with off-season. No seasonal differences in the T-cell numbers in these patients were seen. Off-season, there was no significant difference between the patients and the control subjects regarding the intestinal frequencies of MBP+ eosinophils, mucosal IgE+ cells, and T cells. CONCLUSION: Birch pollen exposure triggered a local inflammation with an increase in duodenal eosinophils and IgE-carrying mast cells in patients with allergy. Our study gives evidence for the interplay between immunologically active cells in the airways and the gut.

Adult↗
PubMed2003

The transfer of immunity from mother to child.

The newborn's immune system grows fast from a small size at birth by exposure primarily to the intestinal microflora normally obtained from the mother at and after birth. While building up its immune system, the infant is supported by the transplacental IgG antibodies, which also contain anti-idiotypic antibodies, possibly also actively priming the offspring. The second mode of transfer of immunity occurs via the milk. Numerous major protective components, including secretory IgA (SIgA) antibodies and lactoferrin, are present. The breastfed infant is better protected against numerous common infections than the non-breastfed. Breastfeeding also seems to actively stimulate the infant's immune system by anti-idiotypes, uptake of milk lymphocytes, cytokines, etc. Therefore, the breastfed child continues to be better protected against various infections for some years. Vaccine responses are also often enhanced in breastfed infants. Long-lasting protection against certain immunological diseases such as allergies and celiac disease is also noted.

Female↗
PubMed2002

Local allergic reaction in food-hypersensitive adults despite a lack of systemic food-specific IgE.

BACKGROUND: Objective tools are lacking for the diagnosis of local gastrointestinal inflammatory reactions in skin prick test (SPT)-negative and serum IgE antibody (s-IgE Ab)-negative patients with suspected food allergy. OBJECTIVE: The purpose of this investigation was to evaluate the presence of eosinophils, T cells, local IgE-bearing cells, IL-4, and IFN-gamma in small intestinal biopsy specimens from adult SPT-negative/s-IgE Ab-negative patients with food allergy during symptomatic and nonsymptomatic periods. METHODS: Fourteen patients with food allergy-related gastrointestinal symptoms confirmed by double-blinded, placebo-controlled food challenge (DBPCFC) were investigated. Eleven of the patients were SPT-negative and s-IgE Ab-negative. Sex- and age-matched healthy volunteers were used as controls. Duodenal biopsies were studied with immunostaining through use of a panel of mouse monoclonal antibodies specific for eosinophils, CD3, CD4, CD8, IgE, IL-4, and IFN-gamma. RESULTS: Significant increases in numbers of MBP+ eosinophils, IgE-bearing cells, and T cells were found in the duodenal mucosa of the patients when they were symptomatic in comparison with when they were asymptomatic and in comparison with healthy controls. Numbers of IL-4+ cells were increased and numbers of IFN-gamma+ cells were reduced in the patients when they were symptomatic in comparison with when they were asymptomatic and in comparison with the controls. There were no differences in total s-IgE levels between any of the groups. CONCLUSION: A significant correlation was found between the appearance of symptoms of food hypersensitivity and the duodenal presence of IgE-bearing cells, activated eosinophils, and T cells in patients with negative SPT results and negative s-IgE Ab to the offending food. We suggest that a localized IgE-mediated response caused the gastrointestinal symptoms seen in these patients.

Adult↗
PubMed2002

Breast-feeding, a complex support system for the offspring.

The newborn has an immune system, very limited in size at birth and its postnatal expansion and maturation takes time. In the meantime the transplacental IgG antibodies from the mother play an important role for the protection of the infant. However, these antibodies act in tissues and induce inflammation and are energy-consuming. In contrast, the milk secretory IgA antibodies stop microbes already on the mucosa preventing infection, tissue engagement and energy loss. In addition, the milk contains many protective factors such as lactoferrin and oligosacharides functioning as analogues for microbial receptors preventing mucosal attachment, the initial step of most infections. As a result, breast-feeding significantly reduces the risk of neonatal septicemia, respiratory tract infections, otitis media, diarrhea, urinary tract infections, infection-induced wheezing and necrotizing enterocolitis. Via several mechanisms it seems that human milk can actively stimulate the immune system of the breast-fed infant. This reduces the risk of infections like otitis media, respiratory tract infections, diarrhea and infection-induced wheezing for several years after the termination of breast-feeding. Furthermore, it seems that breast-feeding decreases the risk of attracting celiac disease and allergic diseases. The latter has been much debated, but a recent critical review of published reports gives good support for long-term protection of allergic diseases, especially in high-risk children.

Breast Feeding↗