Oral tolerance

Faria, Ana Maria Caetano; Weiner, Howard L.

doi:10.1111/j.0105-2896.2005.00280.x

Cited by 634 publications

(632 citation statements)

References 318 publications

(375 reference statements)

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“…Firstly, it reveals a regulatory role for TGF-b, paralelleling a similar role for this cytokine in CD4 + Treg [8,9,14]. This finding nicely places these CD8 + cells into the regulatory family.…”

mentioning

confidence: 89%

“…CD25 -T cells can acquire Foxp3 expression and suppressive capacity after antigen encounter [10][11][12], but it is also clear that Foxp3 is not necessary for suppressive capacity in peripheral Treg [13]. In general, the emerging picture of the peripherally induced Treg is more vague and complex compared to that relating to naturally occurring Treg and many peripherally induced Treg are presently defined according to the cytokines they produce [8,13,14].…”

mentioning

confidence: 99%

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Induced peripheral regulatory T cells: The family grows larger

Höglund

2006

Eur J Immunol

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In order to control immune reactions and to prevent autoimmunity, the immune system relies on a multitude of regulatory T cells (Treg). Most work in this field has focussed on Treg of the CD4 + T cell subset because of the central role CD4 + T cells play as initiators and regulators of immune responses. One discovery of particular importance was the identification of naturally occurring CD4 + CD25 + Treg that arise in the thymus and express the transcription factor Foxp3; however, Treg can also be induced in the periphery after immune activation. A paper in this issue of the European Journal of Immunology identifies a novel type of induced murine CD8 + Treg that arise in TCR HY transgenic female mice after injection of MHC class I tetramers loaded with HY peptide. These Treg prevent subsequent rejection of male skin grafts suggesting that their manipulation may represent a new way of improving graft rejections against minor histocompatibility barriers. Humans have developed two principally different mechanisms to secure self tolerance: thymic negative selection and extrathymic control by specialized T cells with potential regulatory capacity. In the first process, developing T cell precursors that happen to express an autoreactive TCR are deleted. Thymic negative selection is also surprisingly efficient against tissue-specific antigens. The reason for this is the presence of a unique transcription factor, autoimmune regulator (AIRE), that operates in rare antigen-presenting cells in the thymic medulla [1]. AIRE liberates expression of tissue-specific antigens and, in this way, allows negative selection of autoreactive thymocytes. The importance of the AIRE gene for negative selection is illustrated by the large range of autoimmune manifestations that result from a lack of AIRE function [2,3].Even if negative selection operates normally, autoreactive T cells nevertheless escape from the thymus, circulate in the blood and seed the peripheral lymphoid organs; however, while autoreactive T cells can be detected in all individuals upon in vitro re-stimulation, not all people develop autoimmune diseases. One reason for this is the existence of peripheral tolerance mechanisms that keep autoreactive cells in check. Of these, so called "regulatory T cells" (Treg) attract much attention. The most studied Treg is the CD4 + CD25 + cell, also called naturally arising regulatory T cells [4]. These cells originate in the thymus and are identified by the activity of the transcription factor Foxp3 [5]. CD4 + CD25 + Foxp3 + Treg exit from the mouse thymus

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confidence: 89%

mentioning

confidence: 99%

Induced peripheral regulatory T cells: The family grows larger

Höglund

2006

Eur J Immunol

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“…In the pre-clinical trials investigators were able to show that oral adminstration of myelin induced circulating myelin basic protein and proteolipid protein Th3 T cells capable of secreting transforming growth factor-Beta 1. 14 The major immunodominant T and B cell epitope for myelin basic protein lies between residues 82 and 99. 22,23 Intravenous administration of injection of myelin basic protein peptide 82-98, containing the immunodominant region VVHFFKNIVT, in a phase 1 trial lead to tolerance, with the absence of antibodies to myelin basic protein in the spinal fluid for up to 4 months.…”

Section: Trials With Native Myelin Proteins and Native Myelin Peptidesmentioning

confidence: 99%

“…7 In this article I shall explore four ongoing examples where investigators are attempting antigen specific approaches for the treatment of MS: two trials with the same altered peptide ligand directed to the 83-99 peptide of myelin basic protein 8,9 ; a trial of therapy with a peptide to myelin basic protein 82-98 10 ; and a trial of a DNA vaccine directed to the entire myelin basic protein molecule. 11 Earlier attempts by Jonas Salk and colleagues to tolerize the immune system with porcine myelin basic protein, 12,13 and by Weiner and colleagues 14 to tolerize via orally delivering myelin antigens will be discussed in context.…”

Section: Introductionmentioning

confidence: 99%

Antigen-Specific Therapy of Multiple Sclerosis: The Long-Sought Magic Bullet

Steinman

2007

Neurotherapeutics

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Summary:The adaptive immune response in multiple sclerosis (MS) targets various myelin proteins and even some inducible heat shock proteins. A few attempts have been made to tolerize relapsing-remitting patients with MS to either fulllength myelin basic protein or to a key peptide epitope between residues 83-99. These trials have demonstrated that this approach may potentially provide benefit to patients with relapsing-remitting MS. However, manipulation of responses to myelin proteins can have deleterious effects. The immune response to myelin components is positioned at a key tipping point in the pathophysiology of the disease. Clarification of the key target antigens in MS, and better understanding of practical methods to attain tolerance to a wide variety of myelin and neuronal molecules will provide the basis for the ultimately successful antigen specific therapy.

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“…For example, the administration of an oral antigen suppresses autoimmune diseases in animal models including experimental autoimmune encephalitis, arthritis and non-autoimmune diseases such as asthma, allergy, stroke and Alzheimer's disease. 5 Several mechanisms of oral tolerance have been proposed: deletion of antigen-specific T cells (clonal deletion), 6 immune deviation, 7 induction of anergy 8 and suppression of antigen-reactive cells by regulatory T cells (Tregs). 9 In clinical settings, oral tolerance has been used to treat allergic diseases.…”

Section: Introductionmentioning

confidence: 99%

Construction of a Der p2-transgenic plant for the alleviation of airway inflammation

et al. 2011

Cell Mol Immunol

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In clinical therapy, the amount of antigen administered to achieve oral tolerance for allergic diseases is large, and the cost is a major consideration. In this study, we used tobacco plants to develop a large-scale protein production system for allergen-specific immunotherapy, and we investigated the mechanisms of oral tolerance induced by a transgenic plant-derived antigen. We used plants (tobacco leaves) transgenic for the Dermatophagoides pteronyssinus 2 (Der p2) antigen to produce Der p2. Mice received total protein extract from Der p2 orally once per day over 6 days (days 0-2 and days 6-8). Mice were also sensitized and challenged with yeast-derived recombinant Der p2 (rDer p2), after which the mice were examined for airway hyper-responsiveness and airway inflammation. After sensitization and challenge with rDer p2, mice that were fed with total protein extracted from transgenic plants showed decreases in serum Der p2-specific IgE and IgG1 titers, decreased IL-5 and eotaxin levels in bronchial alveolar lavage fluid, and eosinophil infiltration in the airway. In addition, hyper-responsiveness was also decreased in mice that were fed with total protein extracted from transgenic plants, and CD4 1 CD25 1 Foxp3 1 regulatory T cells were significantly increased in mediastinal and mesenteric lymph nodes. Furthermore, splenocytes isolated from transgenic plant protein-fed mice exhibited decreased proliferation and increased IL-10 secretion after stimulation with rDer p2. The data here suggest that allergen-expressing transgenic plants could be used for therapeutic purposes for allergic diseases.

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Oral tolerance

Cited by 634 publications

References 318 publications

Induced peripheral regulatory T cells: The family grows larger

Induced peripheral regulatory T cells: The family grows larger

Antigen-Specific Therapy of Multiple Sclerosis: The Long-Sought Magic Bullet

Construction of a Der p2-transgenic plant for the alleviation of airway inflammation

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