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Oral Tolerance (oral + tolerance)
Terms modified by Oral Tolerance Selected AbstractsNKT cells play critical roles in the induction of oral tolerance by inducing regulatory T cells producing IL-10 and transforming growth factor ,, and by clonally deleting antigen-specific T cellsIMMUNOLOGY, Issue 1 2006Hyun Jung Kim Summary Oral tolerance is the systemic unresponsiveness induced by orally administered proteins. To explore the roles of natural killer T (NKT) cells in oral tolerance, we induced oral tolerance to ovalbumin (OVA) in NKT cell-deficient mice. In CD1d,/, mice, the induction of tolerance to orally administered high- or low-dose OVA was impaired. Dendritic cells (DCs) in the Peyer's patches (PPs) of CD1d,/, mice fed OVA showed high expression of major histocompatibility complex (MHC) class II and B7 molecules, whereas DCs of control mice fed OVA expressed low levels of these molecules. The adoptive transfer of NKT cells restored oral tolerance and induction of tolerogenic DCs in the PPs and spleens of CD1d,/, mice. Moreover, interleukin (IL)-10 and transforming growth factor (TGF)-,1 production in vitro were reduced in cells from the spleen and PPs of CD1d,/, mice compared with those of control mice fed OVA. The numbers of OVA-specific CD4+ KJ1-26+ T cells were significantly reduced in the PPs and spleens of DO11·10 mice fed OVA. In contrast, OVA-specific CD4+ KJ1-26+ T cells were not deleted in the PPs or spleens of DO11·10 CD1d,/, mice. In conclusion, NKT cells were found to play an indispensable role in oral tolerance by inducing regulatory T cells, and clonally deleting antigen-specific CD4+ T cells. [source] Interleukin-15 is not required for the induction or maintenance of orally induced peripheral toleranceIMMUNOLOGY, Issue 3 2004Owain R. Millington Summary Orally induced tolerance is a physiologically relevant form of peripheral tolerance, which is believed to be important for the prevention of pathological immune responses in the gut. Of several mechanisms proposed to mediate oral tolerance, one that has received much attention recently is the concept of regulatory CD4+ T cells. As recent studies have suggested that interleukin (IL)-15 may be important for the differentiation and maintenance of regulatory CD4+ T cells, we have examined the role of IL-15 in oral tolerance, using a soluble form of the IL-15 receptor (sIL-15R) which blocks the biological effects of IL-15 in vivo. Oral tolerance induced by feeding mice ovalbumin (OVA) in a low-dose regimen believed to induce regulatory T cell activity was not affected by the administration of sIL-15R during either the induction or maintenance phase of tolerance. Thus, oral tolerance does not involve an IL-15-dependent mechanism. [source] Role of NK1.1+ and AsGm-1+ cells in oral immunoregulation of experimental colitisINFLAMMATORY BOWEL DISEASES, Issue 2 2003Shivti Trop Abstract NK1.1 and AsGm-1 expressing cells play a role in immunomodulation. Our purpose was to determine the role of NK1.1+ and AsGm-1+ expressing cells in the inflammatory/tolerance paradigm in experimental colitis. Oral tolerance towards colitis-extracted proteins had previously been shown to alleviate experimental colitis. Colitis was induced in C57/B6 mice by intracolonic instillation of trinitrobenzenesulfonic acid (TNBS). Oral tolerance was induced via five oral doses of proteins extracted from TNBS-colitis colonic wall. Clinical, macroscopic, and microscopic scores were used for colitis assessment. To evaluate the putative role of AsGm-1 in tolerance induction, depletion of AsGm-1 expressing cells was performed. To evaluate the mechanism of tolerance induction, liver-associated NKT lymphocytes were harvested 14 days following tolerance induction, and cultured with concanavalin A (con A) and colitis-extracted proteins. T cell subsets were measured by flow cytometry. Cytokine expression was measured by intracellular staining and enzyme-linked immunosorbent assay (ELISA). Orally tolerized mice exhibited significant alleviation of the clinical, macroscopic, and microscopic parameters of colitis, with increased CD4+IL4+/CD4+IFN,+ lymphocyte ratio, increased IL-4, and decreased IFN, and IL-12 serum levels. In contrast, orally fed mice that were AsGm-1 depleted showed evidence of severe colitis. These mice exhibited significant decreased CD4+IL4+/CD4+IFN,+ ratios, and an increase in IFN, and IL-12, with decreased IL-4 levels. NKT cells harvested from tolerized mice secreted high levels of antiinflammatory cytokines. In contrast, in nontolerized mice, NKT cells mainly secreted proinflammatory cytokines. In a tolerized environment, both NK1.1 and AsGm-1 expressing cells are essential for disease alleviation. In contrast, in a nontolerized environment, AsGm-1 expressing cells support an antiinflammatory immune paradigm, while NKT lymphocytes support a proinflammatory shift. [source] Hypersensitivity and oral tolerance in the absence of a secretory immune systemALLERGY, Issue 5 2010M. R. Karlsson To cite this article: Karlsson M-R, Johansen F-E, Kahu H, Macpherson A, Brandtzaeg P. Hypersensitivity and oral tolerance in the absence of a secretory immune system. Allergy 2010; 65: 561,570. Abstract Background:, Mucosal immunity protects the epithelial barrier by immune exclusion of foreign antigens and by anti-inflammatory tolerance mechanisms, but there is a continuing debate about the role of secretory immunoglobulins (SIgs), particularly SIgA, in the protection against allergy and other inflammatory diseases. Lack of secretory antibodies may cause immune dysfunction and affect mucosally induced (oral) tolerance against food antigens. Methods:, We used polymeric Ig receptor (pIgR) knockout (KO) mice, which cannot export SIgA or SIgM, to study oral tolerance induction by ovalbumin (OVA) feeding and for parenteral antigen sensitization in the same animal. Results:, Remarkable systemic hyperreactivity was observed in pIgR KO mice, as 50% died after intradermal OVA challenge, which was not seen in similarly sensitized and challenged wild-type (WT) mice. Oral tolerance induced by OVA completely protected the sensitized pIgR KO mice against anaphylaxis and suppressed antibody levels (particularly IgG1) as well as delayed-type hypersensitivity (DTH) to OVA. Delayed-type hypersensitivity to a bystander antigen, human serum albumin, was also suppressed and T-cell proliferation against OVA in vitro was reduced in tolerized compared with non-tolerized pIgR KO mice. This effect was largely mediated by CD25+ T cells. Adoptive transfer of splenic putative regulatory T cells (CD4+ CD25+) obtained from OVA-fed pIgR KO mice to naïve WT mice mediated suppression of DTH against OVA after sensitization of the recipients. Conclusion:, Compensatory regulatory T-cell function becomes critical in pIgR-deficient mice to avoid the potentially catastrophic effects of systemic immune hyperreactivity, presumably resulting from defective secretory antibody-mediated immune exclusion of microbial components. [source] Oral tolerance induction to Dermatophagoides pteronyssinus and Blomia tropicalis in sensitized mice: occurrence of natural autoantibodies to immunoglobulin ECLINICAL & EXPERIMENTAL ALLERGY, Issue 11 2002M. N. Sato Summary Background The dust mites Dermatophagoides pteronyssinus (Dp) and Blomia tropicalis (Bt) are important sources of indoor allergens in tropical and subtropical countries. Murine models allow the analysis of the immune response and regulation of IgE production to Dp and Bt allergens. Oral tolerance induces unresponsiveness in naive animals, but its application in sensitized animals can provide useful information to improve allergy therapy. Objective To study the profile of IgE and IgG subclasses antibody upon oral administration with Bt and Dp extract in previously sensitized mice. Further, the occurrence of autoantibodies IgG anti-IgE in the immunization and in the oral tolerance was investigated. Methods A/Sn mice were immunized with Bt or Dp extract in alum, orally administrated with 0.25 mg of Bt or Dp extract or PBS at the 6th, 7th and 8th days after immunization and boosted twice with their respective allergens. To analyse the mice groups, specific IgE antibodies were measured by passive anaphylaxis reaction and specific IgG subclasses and anti-IgE IgG autoantibody by ELISA assay. Results IgE levels were markedly increased in Bt-immunized mice compared with Dp-immunized mice. A distinct profile of the specific isotypes was verified in Bt-immunized mice with a preferential production of IgG3 and IgA antibodies, whereas Dp-immunized mice developed high titres of anti-Dp IgG1, IgG2a and IgG2b antibodies. The antigen feeding inhibited IgE response in both fed-mice groups but only Dp-fed mice presented decreased levels of IgG antibodies. Free anti-IgE IgG autoantibodies were detected mainly in the Dp-immunization and they correlated with the antibody isotypes found against the allergen. Conclusions This is the first time that the murine-type I hypersensitivity is employed to study Bt-immunization, showing a marked IgE production, associated with IgG response, which is at least in part driven by T-independent antigens. The oral tolerance protocol in previously sensitized animals was able to down-modulate IgE response and points out this route as a strategy for allergy therapy. [source] Neonatal exposure to staphylococcal superantigen improves induction of oral tolerance in a mouse model of airway allergyEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2009Anna Lönnqvist Abstract The hygiene hypothesis suggests that lack of microbial stimulation in early infancy may lead to allergy, but it has been difficult to identify particular protective microbial exposures. We have observed that infants colonised in the first week(s) of life with Staphylococcus aureus have lower risk of developing food allergy. As many S. aureus strains produce superantigens with T-cell stimulating properties, we here investigate whether neonatal mucosal exposure to superantigen could influence the capacity to develop oral tolerance and reduce sensitisation and allergy. BALB/c mice were exposed to staphylococcal enterotoxin A (SEA) as neonates and fed with OVA as adults, prior to sensitisation and i.n. OVA challenge. Our results show that SEA pre-treated mice are more efficiently tolerised by OVA feeding, as shown by lower lung-cell infiltration and antigen-specific IgE response in the SEA pre-treated mice, compared with sham-treated mice. This was not due to deletion or anergy of lymphocytes by SEA treatment, because the SEA pre-treated mice that were fed with PBS showed similar inflammatory response as the sham-treated PBS-fed mice. Our results suggest that strong T-cell activation in infancy conditions the mucosal immune system and promotes development of oral tolerance. [source] NKT cells are dispensable in the induction of oral tolerance but are indispensable in the abrogation of oral tolerance by prostaglandin EEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2003Ryotaro Ishimitsu Abstract NK1.1+ ,,, T cells (NKT cells) regulate the Th1/Th2 balance in response to dietary Ag, which may be involved in regulation of oral tolerance. OVA-specific IgE and IgG1 Ab levels were significantly lower following an i.p. injection of OVA (in CFA) in C57BL/6 mice orally given a single, high dose (25,mg) of OVA than in those orally given PBS. The oral tolerance was normally induced in J,281,/, mice which lack V,14+ NKT cells, suggesting that NKT cells are dispensable for induction of oral tolerance. Treatment with PGE1 or PGE2 abrogated the oral tolerance in J,281+/+ mice; this abrogation was accompanied by an OVA-specific Th2-dominant response. The abrogation of oral tolerance by PGE1 was not evident in J,281,/, mice. Treatment with PGE1 induced an early increase in IL-4 production by liver NKT cells in normal mice and neutralization of the early IL-4 by administration of anti-IL-4 mAb abolished PGE1 -induced abrogation of oral tolerance. These results suggest that liver NKT cells producing IL-4 are responsible for the down-regulation of oral tolerance that is caused by the PGE molecules. [source] Induction and mechanism of action of transforming growth factor-,-secreting Th3 regulatory cellsIMMUNOLOGICAL REVIEWS, Issue 1 2001Howard L. Weiner Summary: Th3 CD4+ regulatory cells were identified during the course of investigating mechanisms associated with oral tolerance. Different mechanisms of tolerance are induced following oral antigen administration, including active suppression, clonal anergy and deletion. Low doses favor active suppression whereas high doses favor anergy/deletion. Th3 regulatory cells form a unique T-cell subset which primarily secretes transforming growth factor (TGF)-,, provides help for IgA and has suppressive properties for both Th1 and Th2 cells. Th3 type cells are distinct from the Th2 cells, as CD4+ TGF-,-secreting cells with suppressive properties have been generated from interleukin (IL)-4-deficient animals. In vitro differentiation of Th3 cells from Th precursors from T-cell antigen receptor (TCR) transgenic mice is enhanced by culture with TGF-,, IL-4, IL-10, and anti-IL-12. Th3 CD4+ myelin basic protein regulatory clones are structurally identical to Th1 encephalitogenic clones in TCR usage, MHC restriction and epitope recognition, but produce TGF-, with various amounts of IL-4 and IL-10. Because Th3 regulatory cells are triggered in an antigen-specific fashion but suppress in an antigen-non-specific fashion, they mediate "bystander suppression" when they encounter the fed autoantigen at the target organ. In vivo induction of Th3 cells and low dose oral tolerance is enhanced by oral administration of IL-4. Anti-CD86 but not anti-CD80 blocks the induction of Th3 cells associated with low dose oral tolerance. Th3 regulatory cells have been described in other systems (e.g. recovery from experimental allergic encephalomyelitis) but may be preferentially generated following oral antigen administration due to the gut immunologic milieu that is rich in TGF-, and has a unique class of dendritic cells. CD4+CD25+ regulatory T-cell function also appears related to TGF-,. [source] NKT cells play critical roles in the induction of oral tolerance by inducing regulatory T cells producing IL-10 and transforming growth factor ,, and by clonally deleting antigen-specific T cellsIMMUNOLOGY, Issue 1 2006Hyun Jung Kim Summary Oral tolerance is the systemic unresponsiveness induced by orally administered proteins. To explore the roles of natural killer T (NKT) cells in oral tolerance, we induced oral tolerance to ovalbumin (OVA) in NKT cell-deficient mice. In CD1d,/, mice, the induction of tolerance to orally administered high- or low-dose OVA was impaired. Dendritic cells (DCs) in the Peyer's patches (PPs) of CD1d,/, mice fed OVA showed high expression of major histocompatibility complex (MHC) class II and B7 molecules, whereas DCs of control mice fed OVA expressed low levels of these molecules. The adoptive transfer of NKT cells restored oral tolerance and induction of tolerogenic DCs in the PPs and spleens of CD1d,/, mice. Moreover, interleukin (IL)-10 and transforming growth factor (TGF)-,1 production in vitro were reduced in cells from the spleen and PPs of CD1d,/, mice compared with those of control mice fed OVA. The numbers of OVA-specific CD4+ KJ1-26+ T cells were significantly reduced in the PPs and spleens of DO11·10 mice fed OVA. In contrast, OVA-specific CD4+ KJ1-26+ T cells were not deleted in the PPs or spleens of DO11·10 CD1d,/, mice. In conclusion, NKT cells were found to play an indispensable role in oral tolerance by inducing regulatory T cells, and clonally deleting antigen-specific CD4+ T cells. [source] A novel model of sensitization and oral tolerance to peanut proteinIMMUNOLOGY, Issue 3 2004Jessica Strid Summary The prevalence of food allergic diseases is rising and poses an increasing clinical problem. Peanut allergy affects around 1% of the population and is a common food allergy associated with severe clinical manifestations. The exact route of primary sensitization is unknown although the gastrointestinal immune system is likely to play an important role. Exposure of the gastrointestinal tract to soluble antigens normally leads to a state of antigen-specific systemic hyporesponsiveness (oral tolerance). A deviation from this process is thought to be responsible for food-allergic diseases. In this study, we have developed a murine model to investigate immunoregulatory processes after ingestion of peanut protein and compared this to a model of oral tolerance to chicken egg ovalbumin (OVA). We demonstrate that oral tolerance induction is highly dose dependent and differs for the allergenic proteins peanut and OVA. Tolerance to peanut requires a significantly higher oral dose than tolerance to OVA. Low doses of peanut are more likely to induce oral sensitization and increased production of interleukin-4 and specific immunoglobulin E upon challenge. When tolerance is induced both T helper 1 and 2 responses are suppressed. These results show that oral tolerance to peanut can be induced experimentally but that peanut proteins have a potent sensitizing effect. This model can now be used to define regulatory mechanisms following oral exposure to allergenic proteins on local, mucosal and systemic immunity and to investigate the immunomodulating effects of non-oral routes of allergen exposure on the development of allergic sensitization to peanut and other food allergens. [source] Interleukin-15 is not required for the induction or maintenance of orally induced peripheral toleranceIMMUNOLOGY, Issue 3 2004Owain R. Millington Summary Orally induced tolerance is a physiologically relevant form of peripheral tolerance, which is believed to be important for the prevention of pathological immune responses in the gut. Of several mechanisms proposed to mediate oral tolerance, one that has received much attention recently is the concept of regulatory CD4+ T cells. As recent studies have suggested that interleukin (IL)-15 may be important for the differentiation and maintenance of regulatory CD4+ T cells, we have examined the role of IL-15 in oral tolerance, using a soluble form of the IL-15 receptor (sIL-15R) which blocks the biological effects of IL-15 in vivo. Oral tolerance induced by feeding mice ovalbumin (OVA) in a low-dose regimen believed to induce regulatory T cell activity was not affected by the administration of sIL-15R during either the induction or maintenance phase of tolerance. Thus, oral tolerance does not involve an IL-15-dependent mechanism. [source] The Th1/Th2 immune-type response of the recurrent aphthous ulceration analyzed by cDNA microarrayJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 3 2004R. C. Borra Background:, The reduced ability to activate oral tolerance plays a role in the pathogenesis of some gastrointestinal inflammatory diseases. This activation may reflect a preferential reduction of a T-helper (Th)2- or Th3-type response. In recurrent aphthous ulceration (RAU), genetic and environmental factors may contribute to low tolerance, permitting a cytotoxic reaction against the oral epithelium. The cytokine profile has not permitted the definition of RAU as resulting from enhanced Th1 or Th2 responses. A cDNA microarray study would allow the identification of differentially expressed genes and provide a basis for classification of the immune response. Methods:, The cDNA from 29 samples of aphthae and from 11 samples of normal mucosa from aphthae-free volunteers were hybridized on microarray membranes with 1176 genes. Results:, Forty-one differentially expressed genes were identified, and a higher expression level of the Th1 gene cluster in RAU was found. Conclusions:, Microarrays permitted us definition of the gene expression profile of the lesion and identify an increased Th1 activity in RAU lesions. [source] Allergy to peanut oil , clinically relevant?JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 4 2007J Ring Abstract The increasing prevalence of food allergies (especially allergy to peanuts) has led to a discussion of how safe topical preparations containing peanut oil are with respect to allergy. The major allergens from peanuts are proteins that have been characterized at a molecular level and cloned. Clinical signs of peanut allergy symptoms can be observed on the skin (urticaria), or in the gastrointestinal and/or respiratory tract culminating in cardiovascular symptoms and anaphylactic reactions. In most cases, symptoms are elicited by oral uptake; rarely, a contact urticaria has been described. In vegetable oils, the contents of protein differ depending on the production process: crude oils contain approximately 100 times more proteins than refined oils. This has clear-cut implications for allergic individuals. Quantitative data are available regarding elicitation of symptoms in allergic individuals with a threshold dose of 0.1,1 mg peanut allergen in oral provocation tests. There are anecdotal reports of adverse reactions after topical use of peanut oils. In one epidemiological trial, an association between topical use of skin care products containing peanut oil and the development of peanut allergy was observed; however, the data reflect a retrospective analysis without specifying skin care products containing peanut oil and also without analysing the quantity of topicals used. In contrast, oral tolerance was prevented and allergic sensitization was enhanced in a mouse model using high concentrations of peanut protein. So far, no reliable data are available regarding doses required to induce sensitization against peanut allergen via the epidermal route. A possible induction of sensitization against peanut proteins through contact with the skin via skin care products and the respective protein concentrations is a matter of speculation. Patients with atopic diseases, namely eczema, need appropriate skin care because of the disturbed skin barrier function. The benefit of avoiding damage to skin barrier functions of atopic individuals by the use of peanut protein-containing skin care products seems to outweigh possible risks of sensitization and/or allergy induction against substances contained in those products containing refined peanut oil. [source] Suppression of immune responses to ,-lactoglobulin in mice by the oral administration of peptides representing dominant T cell epitopesJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 3 2008Koko Mizumachi Abstract BACKGROUND: The significance of oral tolerance in the treatment of adverse immune reactions such as allergic and autoimmune diseases has been noted. In the present study, peptides that could effectively induce oral tolerance to bovine ,-lactoglobulin (BLG), a milk allergen, were investigated in a murine model. RESULTS: The oral administration of peptides corresponding to the T cell epitope regions of BLG, i.e. p42,56, p62,76 and p139,154, apparently down-regulated T cell proliferation to BLG. The in vitro cytokine production by the lymph node cells from the peptide-fed mice cultured in the presence of the antigen was also analysed. It was found that p62,76 and p139,154 feeding suppressed the production of both Th1 and Th2 types. Interestingly, p139,154 feeding suppressed both T cell and antibody responses to BLG. Additionally, p139,154 feeding diminished BLG-specific IgE and IgG1 antibody responses. CONCLUSION: The unique tolerogen peptide p139,154 that could suppress both T and B cell responses to BLG in a murine model was identified. These findings can be useful for the selection of an optimum tolerogenic peptide to prevent and treat milk and other food allergies. Copyright © 2007 Society of Chemical Industry [source] Hypersensitivity and oral tolerance in the absence of a secretory immune systemALLERGY, Issue 5 2010M. R. Karlsson To cite this article: Karlsson M-R, Johansen F-E, Kahu H, Macpherson A, Brandtzaeg P. Hypersensitivity and oral tolerance in the absence of a secretory immune system. Allergy 2010; 65: 561,570. Abstract Background:, Mucosal immunity protects the epithelial barrier by immune exclusion of foreign antigens and by anti-inflammatory tolerance mechanisms, but there is a continuing debate about the role of secretory immunoglobulins (SIgs), particularly SIgA, in the protection against allergy and other inflammatory diseases. Lack of secretory antibodies may cause immune dysfunction and affect mucosally induced (oral) tolerance against food antigens. Methods:, We used polymeric Ig receptor (pIgR) knockout (KO) mice, which cannot export SIgA or SIgM, to study oral tolerance induction by ovalbumin (OVA) feeding and for parenteral antigen sensitization in the same animal. Results:, Remarkable systemic hyperreactivity was observed in pIgR KO mice, as 50% died after intradermal OVA challenge, which was not seen in similarly sensitized and challenged wild-type (WT) mice. Oral tolerance induced by OVA completely protected the sensitized pIgR KO mice against anaphylaxis and suppressed antibody levels (particularly IgG1) as well as delayed-type hypersensitivity (DTH) to OVA. Delayed-type hypersensitivity to a bystander antigen, human serum albumin, was also suppressed and T-cell proliferation against OVA in vitro was reduced in tolerized compared with non-tolerized pIgR KO mice. This effect was largely mediated by CD25+ T cells. Adoptive transfer of splenic putative regulatory T cells (CD4+ CD25+) obtained from OVA-fed pIgR KO mice to naïve WT mice mediated suppression of DTH against OVA after sensitization of the recipients. Conclusion:, Compensatory regulatory T-cell function becomes critical in pIgR-deficient mice to avoid the potentially catastrophic effects of systemic immune hyperreactivity, presumably resulting from defective secretory antibody-mediated immune exclusion of microbial components. [source] The role of the intestinal microbiota in the development of atopic disordersALLERGY, Issue 11 2007J. Penders The prevalence of atopic diseases, including eczema, allergic rhinoconjunctivitis and asthma, has increased worldwide, predominantly in westernized countries. Recent epidemiological studies and experimental research suggest that microbial stimulation of the immune system influences the development of tolerance to innocuous allergens. The gastrointestinal microbiota composition may be of particular interest, as it provides an early and major source of immune stimulation and seems to be a prerequisite for the development of oral tolerance. In this review the observational studies of the association between the gut microbiota and atopic diseases are discussed. Although most studies indicated an association between the gut microbiota composition and atopic sensitization or symptoms, no specific harmful or protective microbes can be identified yet. Some important methodological issues that have to be considered are the microbiological methods used (traditional culture vs molecular techniques), the timing of examining the gut microbiota, the definition of atopic outcomes, confounding and reverse causation. In conclusion, the microbiota hypothesis in atopic diseases is promising and deserves further attention. To gain more insight into the role of the gut microbiota in the etiology of atopy, large-scale prospective birth cohort studies using molecular methods to study the gut microbiota are needed. [source] Role of CD4+ and CD8+ T-cells in the induction of oral tolerance to Actinomyces viscosus in miceMOLECULAR ORAL MICROBIOLOGY, Issue 3 2006W. Sosroseno Mucosal presentation of Actinomyces viscosus results in the induction of antigen specific systemic suppressor cells in mice. The aim of the present study was to determine the phenotype of the suppressor cells responsible for the induction of oral tolerance to low doses of A. viscosus. When CD8 cell-depleted DBA/2 mice were intragastrically immunized and systemically immunized with A. viscosus, the delayed type hypersensitivity response was suppressed but not the levels of antigen specific serum antibodies. Adoptive transfer of orally tolerized CD4+ cells to CD4+ -depleted mice resulted in suppression of delayed type hypersensitivity response but not of the levels of antigen specific serum antibodies. In contrast, adoptive transfer of orally immunized CD8+ cells to CD8+ -depleted mice resulted in partially suppressed delayed type hypersensitivity response but significantly inhibited the levels of antigen specific serum antibodies. When orally tolerized CD8+ cells were cocultured with systemically immunized CD8+ cell-depleted spleen cells, splenic specific antibodies were inhibited. However, no suppression of splenic specific antibodies could be observed in the cultures containing orally tolerized CD4+ cells and systemically immunized CD4+ cell-depleted spleen cells. The results of the present study suggest that oral tolerance of humoral and cellular immunity induced by low doses of A. viscosus may be mediated by CD8+ and CD4+ cells, respectively. [source] Abnormalities of IgA1 production in IgA nephropathyNEPHROLOGY, Issue 2002John FEEHALLY SUMMARY: IgA nephropathy (IgAN) is characterized by the mesangial deposition of polymeric IgA1 (plgA1). the original view that this plgA1 is derived from the mucosal immune system can no longer be sustained. Studies of duodenal mucosa and marrow indicate increased production of plgA1 in the marrow and decreased production in the mucosa. These changes are consistent with immunization studies showing exaggerated and prolonged plgA responses to systemic immunization, and reduced mucosal responses to mucosal neoantigens. However, the IgA1 and IgG systemic responses to mucosal antigen are increased in IgAN, a finding consistent with impairment in oral tolerance, the process by which systemic immune responses, to mucosal antigen challenge are normally suppressed. Both IgA1 production and the induction of oral tolerance are under T-cell control. T-cell populations involved in these processes include ,, T cells, Tr cells and T-helper (Th)3 cells; cytokines with a key role in the control of IgA production include interleukin (IL)-10 and transforming growth factor (TGF)-,. There is evidence of abnormal ,, T-cell V region usage in both mucosa and marrow in IgAN. Increased expression of relevant cytokines has also been reported in circulating T cells in IgAN. the increased O-glycosylation of circulating IgA1 in IgAN may also be further evidence of a shift in the production of mucosal-type plgA1 from the mucosa to marrow. These findings suggest that the specific lymphocyte homing mechanisms that normally maintain oral tolerance and control the site of IgA production require further study in IgAN. [source] High intestinal IgA associates with reduced risk of IgE-associated allergic diseasesPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 1-Part-I 2010Kaarina Kukkonen Kukkonen K, Kuitunen M, Haahtela T, Korpela R, Poussa T, Savilahti E. High intestinal IgA associates with reduced risk of IgE-associated allergic diseases. Pediatr Allergy Immunol 2010: 21: 67,73. © 2009 John Wiley & Sons A/S Development of oral tolerance and its stimulation by probiotics are still incomprehensible. Microbial stimulation of the gut may induce a subtle inflammation and induce secretion of mucosal IgA, which participates in antigen elimination. In a cohort of allergy-prone infants receiving probiotics and prebiotics or placebo we studied intestinal IgA and inflammation in the development of eczema, food allergy, asthma, and rhinitis (allergic diseases). We performed a nested unmatched case,control study of 237 infants participating in a randomized double-blind placebo-controlled allergy-prevention trial using a combination of four probiotic strains pre-natally and during 6 months form birth. We measured faecal IgA, ,1-antitrypsin (,1-AT), tumour necrosis factor-alpha (TNF-,), and calprotectin at the age of 3 and 6 months. By age 2 yr, 124 infants had developed allergic disease or IgE-sensitization (cases) and 113 had not (controls). In infants with high faecal IgA concentration at the age of 6 months, the risk of having any allergic disease before the age of 2 yr tended to reduce [odds ratio (OR: 0.52)] and the risk for any IgE-associated (atopic) disease reduced significantly (OR: 0.49). High faecal calprotectin at the age of 6 months associated also with lower risk for IgE-associated diseases up to age 2 yr (OR: 0.49). All faecal inflammation markers (,1-AT, TNF-,, and calprotectin) correlated positively with faecal IgA (p < 0.001). Probiotics tended to augment faecal IgA (p = 0.085) and significantly increased faecal ,1-AT (p = 0.001). High intestinal IgA in early life associates with minimal intestinal inflammation and indicates reduced risk for IgE-associated allergic diseases. [source] The importance of early complementary feeding in the development of oral tolerance: Concerns and controversiesPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 5 2008Susan L. Prescott Rising rates of food allergies in early childhood reflect increasing failure of early immune tolerance mechanisms. There is mounting concern that the current recommended practice of delaying complementary foods until 6 months of age may increase, rather than decrease, the risk of immune disorders. Tolerance to food allergens appears to be driven by regular, early exposure to these proteins during a ,critical early window' of development. Although the timing of this window is not clear in humans, current evidence suggests that this is most likely to be between 4 and 6 months of life and that delayed exposure beyond this period may increase the risk of food allergy, coeliac disease and islet cell autoimmunity. There is also evidence that other factors such as favourable colonization and continued breastfeeding promote tolerance and have protective effects during this period when complementary feeding is initiated. This discussion paper explores the basis for concern over the current recommendation to delay complementary foods as an approach to preventing allergic disease. It will also examine the growing case for introducing complementary foods from around 4 months of age and maintaining breastfeeding during this early feeding period, for at least 6 months if possible. [source] Allergen-specific antibody and cytokine responses, mast cell reactivity and intestinal permeability upon oral challenge of sensitized and tolerized miceCLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2010C. Perrier Summary Background Food allergy has reached an epidemic level in westernized countries and although central mechanisms have been described, the variability associated with genetic diversity underscores the still unresolved complexity of these disorders. Objective To develop models of food allergy and oral tolerance, both strictly induced by the intestinal route, and to compare antigen-specific responses. Methods BALB/c mice were mucosally sensitized to ovalbumin (OVA) in the presence of the mucosal adjuvant cholera toxin, or tolerized by intra-gastric administrations of OVA alone. Antibody titres and cytokines were determined by ELISA, and allergic status was determined through several physiologic parameters including decline in temperature, diarrhoea, mast cell degranulation and intestinal permeability. Results OVA-specific antibodies (IgE, IgGs and IgA in serum and feces) were produced in sensitized mice exclusively. Upon intra-gastric challenge with OVA, sensitized mice developed anaphylactic reactions associated with a decline of temperature, diarrhoea, degranulation of mast cells, which were only moderately recruited in the small intestine, and increased intestinal permeability. Cytokines produced by immune cells from sensitized mice included T-helper type 2 cytokines (IL-5, IL-13), but also IL-10, IFN-, and IL-17. In contrast, all markers of allergy were totally absent in tolerized animals, and yet the latter were protected from subsequent sensitization, demonstrating that oral tolerance took place efficiently. Conclusion This work allows for the first time an appropriate comparison between sensitized and tolerized BALB/c mice towards OVA. It highlights important differences from other models of allergy, and thus questions some of the generally accepted notions of allergic reactions, such as the protective role of IFN-,, the importance of antigen-specific secretory IgA and the role of mucosal mast cells in intestinal anaphylaxis. In addition, it suggests that IL-17 might be an effector cytokine in food allergy. Finally, it demonstrates that intestinal permeability towards the allergen is increased during challenge. Cite this as: C. Perrier, A.-C. Thierry, A. Mercenier and B. Corthésy, Clinical & Experimental Allergy, 2010 (40) 153,162. [source] Dietary allergenic proteins and intestinal immunity: a shift from oral tolerance to sensitizationCLINICAL & EXPERIMENTAL ALLERGY, Issue 2 2008This editorial discusses the findings of the paper in this issue by C. R. Cardoso et al, pp 33 First page of article [source] Primary prevention of allergy: avoiding risk or providing protection?CLINICAL & EXPERIMENTAL ALLERGY, Issue 2 2008E. Hamelmann Summary Primary prevention strategies of allergy so far have been aimed to fight allergy causes, by avoiding risk factors and inhibiting their mechanisms of action. The results of trials testing food or airborne allergen avoidance as a prevention strategy were, however, rather disappointing. A reverse approach for primary prevention of allergies aims to facilitate exposure to protecting factors which promote the induction of immunologic tolerance against innocuous antigens. These factors are associated with farming environment and a ,traditional lifestyle', but identification of these factors is quite difficult. Major candidates include food-borne microbes, helminths or their components, which are able to stimulate mucosal immunity, particularly in the gut. Similarly, new preventive and therapeutic strategies are being tested to induce specific food-allergen oral tolerance through the ingestion of progressively increasing doses of the offending food. This shifting of allergy prevention research from avoidance to tolerance induction will hopefully allow us to reverse the epidemic trend of allergy diseases. [source] The ,microflora hypothesis' of allergic diseasesCLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2005M. C. Noverr Summary Increasingly, epidemiologic and clinical data support the hypothesis that perturbations in the gastrointestinal (GI) microbiota because of antibiotic use and dietary differences in ,industrialized' countries have disrupted the normal microbiota-mediated mechanisms of immunological tolerance in the mucosa, leading to an increase in the incidence of allergic airway disease. The data supporting this ,microflora hypothesis' includes correlations between allergic airway disease and (1) antibiotic use early in life, (2) altered fecal microbiota and (3) dietary changes over the past two decades. Our laboratory has recently demonstrated that mice can develop allergic airway responses to allergens if their endogenous microbiota is altered at the time of first allergen exposure. These experimental and clinical observations are consistent with other studies demonstrating that the endogenous microbiota plays a significant role in shaping the development of the immune system. Data are beginning to accumulate that a ,balanced' microbiota plays a positive role in maintaining mucosal immunologic tolerance long after post-natal development. Other studies have demonstrated that even small volumes delivered to the nasopharynx largely end up in the GI tract, suggesting that airway tolerance and oral tolerance may operate simultaneously. The mechanism of microbiota modulation of host immunity is not known; however, host and microbial oxylipins are one potential set of immunomodulatory molecules that may control mucosal tolerance. The cumulative data are beginning to support the notion that probiotic and prebiotic strategies be considered for patients coming off of antibiotic therapy. [source] Oral tolerance induction to Dermatophagoides pteronyssinus and Blomia tropicalis in sensitized mice: occurrence of natural autoantibodies to immunoglobulin ECLINICAL & EXPERIMENTAL ALLERGY, Issue 11 2002M. N. Sato Summary Background The dust mites Dermatophagoides pteronyssinus (Dp) and Blomia tropicalis (Bt) are important sources of indoor allergens in tropical and subtropical countries. Murine models allow the analysis of the immune response and regulation of IgE production to Dp and Bt allergens. Oral tolerance induces unresponsiveness in naive animals, but its application in sensitized animals can provide useful information to improve allergy therapy. Objective To study the profile of IgE and IgG subclasses antibody upon oral administration with Bt and Dp extract in previously sensitized mice. Further, the occurrence of autoantibodies IgG anti-IgE in the immunization and in the oral tolerance was investigated. Methods A/Sn mice were immunized with Bt or Dp extract in alum, orally administrated with 0.25 mg of Bt or Dp extract or PBS at the 6th, 7th and 8th days after immunization and boosted twice with their respective allergens. To analyse the mice groups, specific IgE antibodies were measured by passive anaphylaxis reaction and specific IgG subclasses and anti-IgE IgG autoantibody by ELISA assay. Results IgE levels were markedly increased in Bt-immunized mice compared with Dp-immunized mice. A distinct profile of the specific isotypes was verified in Bt-immunized mice with a preferential production of IgG3 and IgA antibodies, whereas Dp-immunized mice developed high titres of anti-Dp IgG1, IgG2a and IgG2b antibodies. The antigen feeding inhibited IgE response in both fed-mice groups but only Dp-fed mice presented decreased levels of IgG antibodies. Free anti-IgE IgG autoantibodies were detected mainly in the Dp-immunization and they correlated with the antibody isotypes found against the allergen. Conclusions This is the first time that the murine-type I hypersensitivity is employed to study Bt-immunization, showing a marked IgE production, associated with IgG response, which is at least in part driven by T-independent antigens. The oral tolerance protocol in previously sensitized animals was able to down-modulate IgE response and points out this route as a strategy for allergy therapy. [source] | |||||||||||||||||||||||||