Tolerosome‐induced oral tolerance is MHC dependent

Östman, Sofia; Taube, Maria Beatriz Puzzi; Telemo, Esbjörn

doi:10.1111/j.1365-2567.2005.02245.x

Cited by 81 publications

(84 citation statements)

References 41 publications

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“…This process does not function in the absence of T cells [35], is reduced in efficiency in germ-free mice [4,36] and is dependent on the expression of MHC class II molecules in the intestinal epithelium [37]. SEA feeding induces a massive secretion of IFN-g from IEL, leading to up-regulation of heat shock proteins and MHC class II on the intestinal epithelium [38].…”

Section: Discussionmentioning

confidence: 99%

“…Tolerogenic processing involves coupling of dietary antigen peptides to MHC class II molecules within the intestinal epithelial cell and export of the complex on membranous vesicles called tolerosomes [37,39]. The tolerosomes can be isolated from the blood shortly after feeding of an antigen and induce tolerance upon transfer into naïve recipients [40].…”

Section: Discussionmentioning

confidence: 99%

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Neonatal exposure to staphylococcal superantigen improves induction of oral tolerance in a mouse model of airway allergy

et al. 2009

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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.Key words: Allergic sensitisation . Mucosal immunity . Staphylococcal enterotoxin A . Tolerance Supporting Information available online IntroductionAllergies have increased markedly in Western industrialised countries, where they now afflict every third child. Allergies are linked to wealth, good education and small families, observations that have given rise to the hygiene hypothesis, according to which the developing immune system should be exposed to appropriate microbial stimulation in early childhood in order to mature correctly and for allergies to be avoided [1,2]. The hygiene hypothesis is also supported by experimental data. Germ-free animals are less prone to develop oral Ã These author contributed equally to this work. Eur. J. Immunol. 2009. 39: 447-456 DOI 10.1002 Immunomodulation 447 tolerance than animals reared conventionally [3,4]. Oral tolerance is induced by passage of antigens over the gut mucosa, prevents against both Th1-and Th2-dominated immune responses [5] and includes development of Treg [6,7]. Natural thymic-dependent Treg (CD4 1 CD25 hi FoxP3 1 ) are fundamental in protection against autoimmunity, gut inflammation and IgE responses. This cell subset has reduced functional capacity in germ-free animals [8].The strongest T-cell activators known are the ''superantigens'', exotoxins produced by certain pathogenic bacteria such as Staphylococcus aureus. These include staphylococcal enterotoxin A, B, C, D and E, as well as toxic shock syndrome toxin-1. The superantigen binds to the variable part of the TCR and to the MHC class II molecule, thereby ''mimicking'' antigen recognition, which leads to T-cell activation [9][10][11][12]. As many as 10-30% of all T cells can become activated by a certain superantigen compared with o0...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Neonatal exposure to staphylococcal superantigen improves induction of oral tolerance in a mouse model of airway allergy

et al. 2009

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“…Exosomes derived from immature DCs expressing immunomodulatory cytokines and ligands (i.e., IL-10, IL-4, FasL) have shown a beneficial effect on delayed-type hypersensitivity and inflammation in animal models (Ostman et al, 2005;Tamura et al, 2012).…”

Section: Applications Of Extracellular Membrane Vesicles For Clinicalmentioning

confidence: 99%

Cell-Cell Communication Via Extracellular Membrane Vesicles and Its Role in the Immune Response

Hwang

2013

Molecules and Cells

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The host immune response involves a variety of cell types, including specialized immune and non-immune cells. The delicate coordination among these cells via close communication is central for the proper operation of immune system. Cell-cell communication is mediated by a complex network that includes soluble factors such as cytokines, chemokines, and metabolites exported from cells, as well as membrane-bound receptors and their ligands. Cell-cell communication is also mediated by membrane vesicles (e.g., exosomes, ectosomes), which are either shed by distant cells or exchanged by cells that are making direct contact. Intercellular communication via extracellular membrane vesicles has drawn much attention recently, as they have been shown to carry various biomolecules that modulate the activities of recipient cells. In this review, I will discuss current views on cell-cell communication via extra-cellular membrane vesicles, especially shedded membrane vesicles, and their effects on the control of the immune system.

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“…19,20 The tolerogenic effect of serum obtained shortly after an antigen feed was first described by Strobel et al 6 using a Th1 sensitization as read-out; however, despite great efforts the nature of the tolerizing serum factor was not revealed until recently. 18,20,21 We also monitored the involvement of regulatory T cells in the induction of tolerance in the present model. As described in our results we found a higher frequency of activated CD4 + T cells with a regulatory phenotype in the group receiving the tolerogenic serum.…”

Section: Discussionmentioning

confidence: 99%

“…8 Moreover we have shown that this exosome-mediated tolerance is MHC class II dependent and requires an intact immune system in the fed donor. 18 In the present study we wanted to investigate whether serum-derived exosomes from antigen-fed donors could also protect against allergic airway inflammation in a mouse model of allergic asthma.…”

Section: Introductionmentioning

confidence: 99%

Serum‐derived exosomes from antigen‐fed mice prevent allergic sensitization in a model of allergic asthma

et al. 2008

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SummaryOral tolerance is an active process that starts with sampling of luminal antigens by the intestinal epithelial cells (IEC), followed by processing and assembly with major histocompatibility complex class II and subsequently a release of tolerogenic exosomes (tolerosomes) from the IEC. We have previously shown that tolerosomes can be isolated from serum shortly after an antigen feed, and will potently transfer antigen-specific tolerance to naive recipients. Here we study the capacity of the tolerosomes to protect against allergic sensitization in a mouse model of allergic asthma. Serum or isolated serum exosomes from tolerized BALB/c donor mice were transferred to syngeneic recipients followed by sensitization and intranasal exposure to ovalbumin (OVA). Blood, bronchoalveolar lavage (BAL) and lymph nodes were sampled 24 hr after the final exposure. The number of eosinophils was counted in BAL fluid and the levels of immunoglobulin E (IgE) and OVA-specific IgE were measured in serum. Mediastinal and coeliac lymph nodes were analysed by flow cytometry. The animals receiving serum from OVA-fed mice displayed significantly lower numbers of airway eosinophils and lower serum levels of total IgE as well as of OVA-specific IgE compared with controls. Moreover, the tolerant animals showed a significantly higher frequency of activated T cells with a regulatory phenotype in both mediastinal and coeliac lymph nodes. The results show that serum or isolated serum exosomes obtained from OVA-fed mice and administered intraperitoneally to naive recipient mice abrogated allergic sensitization in the recipients.

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Tolerosome‐induced oral tolerance is MHC dependent

Cited by 81 publications

References 41 publications

Neonatal exposure to staphylococcal superantigen improves induction of oral tolerance in a mouse model of airway allergy

Neonatal exposure to staphylococcal superantigen improves induction of oral tolerance in a mouse model of airway allergy

Cell-Cell Communication Via Extracellular Membrane Vesicles and Its Role in the Immune Response

Serum‐derived exosomes from antigen‐fed mice prevent allergic sensitization in a model of allergic asthma

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