Chapter category: Immunology
Cytokines, Cyclooxygenases and Oral Tolerance
Oral Tolerance: The Response of the Intestinal Mucosa to Dietary Antigens
Edited by: Olivier MorteauISBN: 0-306-47989-3
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Chapter authors:
Olivier Morteau
The intestinal mucosa faces a perpetual challenge: to allow the entry of minerals and nutrients from the lumen while modulating the immune responses to luminal antigens, in order to prevent mucosal inflammation. The immunosuppressive response of the mucosa to food antigens and bacteria of the normal flora is an active response defined as “oral” or mucosal tolerance. Oral tolerance occurs through three distinct mechanisms involving mucosal T cells: T cell clonal anergy, T cell clonal deletion and secretion of immunosuppressive cytokines by regulatory T cells. Regulatory T cells are generated in Peyer’s patches after antigen feeding1-2 and subsequently migrate in the spleen. Regulatory T cells are either CD8+ (cytotoxic) or CD4+ (helper),3 but only CD4+ T cells are required for oral tolerance, since mice genetically deficient in CD8 but not in CD4 can be rendered tolerant by antigen feeding.4,5 CD4+ T cells are subdivided into two T helper (Th) subsets, according to their pattern in cytokine expression. Th1 cells secrete interleukin (IL)-2, interferon (IFN)gamma, and tumor necrosis factor (TNF)-beta and are involved in cell-mediated immunity, whereas Th2 cells secrete IL-4, IL-5, IL-6 and IL-10 and promote humoral immunity and antibody production.6 Prior to differenciation, naive T cells located in the thymus (Th0) can secrete both Th1 or Th2 cytokines. Upon encounter with an antigen, Th0 cells become memory cells that differentiate into either Th1 or Th2 cells. Th1 and Th2 subsets suppress each other’s functions7,8 and are exclusively expressed in response to a specific antigen.9 According to the Th1/Th2 paradigm established in mice, proinflammatory Th1 cytokines are involved in the abrogation of oral tolerance, whereas Th2 cytokines suppress the Th1 response and promote oral tolerance. In human pathologies, such as inflammatory bowel disease (IBD), the dichotomy between Th1- and Th2-type responses is usually less clearcut. IBD is a group of chronic inflammatory affections evolving through alternance of relapses and remissions, which includes ulcerative colitis (UC) and Crohn’s disease (CD). The pathogenesis of IBD remains obscure but clearly involves multiple factors of genetic, immunological and environmental natures. According to the current concept developed in Chapter 8, IBD results from a lack or an abrogation of mucosal tolerance to commensal bacterial antigens in genetically susceptible individuals. The cytokine profile in CD is characterized by an increase in the expression of IL-12, TNF-alpha and IFN-gamma expression, whereas the immune response in UC is associated with enhanced production of IL-5, but not IL-4 or IFN-gamma.10,11 Therefore, CD is commonly associated with a Th1 response, whereas the immune response in UC is closer to a Th2-type response.
Additional chapters from this book:
Clinical Applications of Oral Tolerance
Howard L. Weiner
Oral tolerance has classically been defined as the specific suppression of cellular and/or humoral immune responses to an antigen by prior administration of the antigen by the oral route. It presuma...
Physiopathology of Celiac Disease
Katri Kaukinen, Markku Meki and Pekka Collin
In celiac disease, ingestion of gluten results in T-cell-mediated small bowel mucosal damage characterized by subtotal or severe partial villous atrophy with crypt hyperplasia. A life-long gluten-fr...
Food and Milk Allergies
Mary H. Perdue and Martine Heyman
Oral tolerance is the usual response to antigens encountered via the gut mucosal immune system. However in some individuals, ingestion of food antigens does not result in a down-regulated system, bu...
Induction of Tolerogenic versus Pathogenic Mucosal Immune Responses by Commensal Enteric Bacteria
Dirk Haller and R. Balfour Sartor
Inflammatory bowel diseases (IBD) including ulcerative colitis (UC) and Crohn’s disease (CD) are spontaneously relapsing, immunologically-mediated disorders of the gastrointestinal tract. Microbial ...
IgA and Mucosal Homeostasis
Jesper Reinholdt and Steffen Husby
Mucosal surfaces represent the major interface between host and environment. They constitute the point of entry of most infectious pathogens, and are in contact with potentially injurious antigens p...
Cytokines, Cyclooxygenases and Oral Tolerance
Olivier Morteau
The intestinal mucosa faces a perpetual challenge: to allow the entry of minerals and nutrients from the lumen while modulating the immune responses to luminal antigens, in order to prevent mucosal ...
The Role of T Cells in the Intestinal Mucosa
Giovanni Monteleone and Thomas T. MacDonald
The intestine contains the largest population of T cells in the body. This reflects the fact that the intestine has a large surface area continuously exposed to dietary antigens and microorganisms. ...
A Revisit of Current Dogma for the Cellular and Molecular Basis of Oral Tolerance
Kohtaro Fujihashi, Hirotomo Kato and Jerry R. McGhee
Studies of the cellular and molecular mechanisms for oral tolerance have focused on the central importance of CD4+ T cells and their surface co-stimulatory molecules as well as derived cytokines. In...
Oral Tolerance: An Overview
Allan McI Mowat
The diet of all animals contains a wide variety of proteins of animal and vegetable origin, most of which are potentially antigenic. Contrary to much popular belief, a significant proportion of this...
Structure and Function of the Gastrointestinal Mucosa
Mona Bajaj-Elliott and Ian R. Sanderson
The large mucosal surface of the gastrointestinal tract faces many challenges while maintaining overall body metabolic integrity.1,2 The primary function of the small intestine is to digest and abso...
