Basic-alimentary tractFailure to induce oral tolerance to a soluble protein in patients with inflammatory bowel disease☆
Section snippets
Induction of oral tolerance
The ability to induce tolerance to the neoantigen KLH involved a modification of the protocol established by Husby et al.8 Patients and normal controls were fed KLH (Calbiochem, La Jolla, CA) at a dose of 5, 50, or 250 mg in 5 mL of phosphate-buffered saline on days 0–5 and 10–15. KLH was used because of its prior use in the study by Husby et al.8 as well as its general use as a potent immunogen in in vivo and in vitro studies. On day 26 patients were given 100 μg of KLH (in sterile
Determination of the dose of antigen required for induction of oral tolerance in normal controls
Because one of the goals of this study was to determine whether there was a defect in mucosal immunoregulation in IBD patients, we initially attempted to define low-dose tolerance in humans (the dose that results in the activation of regulatory T cells). The previously published study by Husby et al.8 used only a dose of 50 mg of KLH. Immune responses after Ag feeding were compared with nonfed controls. As seen in Figure 1A, in the absence of oral Ag administration, SC immunization with KLH
Discussion
The hallmark of the mucosal immune system in the gastrointestinal tract is one of generalized immunosuppression and nonresponsiveness.11, 12 This appears to be a direct consequence of the distinct demands placed on the immune system of the gut as opposed to those demands imposed systemically. Oral tolerance is a phenomenon that reflects this immunosuppressed tone. Although tolerance has been well described in inbred mouse models,6, 7 studies relating to oral tolerance in humans have been rare.8
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Immunotherapy of inflammatory bowel disease (IBD) through mesenchymal stem cells
2022, International ImmunopharmacologyCitation Excerpt :Naturally, due to a phenomenon known as oral tolerance, the mucosal immune system does not react with the contents of the intestinal duct as well as food and microbial flora [14]. The reduction of immunological response to a protein previously exposed via the oral route is known as oral tolerance [15]. When food is being consumed orally, protein antigens can be absorbed via the mucosal surfaces of the gastrointestinal system and make physical contact with immune cells in the intestinal lamina propria [16].
Oral tolerance: an updated review
2022, Immunology LettersIntroduction
2022, Microbial Crosstalk with Immune System: New Insights in TherapeuticsMucosal Immunology: An Overview
2016, Pediatric Allergy: Principles and Practice: Third EditionMucosal Vaccines: An Overview
2015, Mucosal Immunology: Fourth EditionImmunopathology of Celiac Disease
2015, Mucosal Immunology: Fourth Edition
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Supported by National Institutes of Health grants AI23504, AI24671, and AI44236, and a grant from Autoimmune Inc., Boston, MA (L.M.). L.C. received a student fellowship award from the CCFA. L.T. was the recipient of a Crohn’s & Colitis Foundation of America research fellowship award.
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A portion of this work appeared as part of the doctoral thesis of T.A.K.