primary prevention of coeliac disease - Associazione Italiana ...

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68 MECHANISMS OF ORAL TOLERANCE types of T cell populations in the intestine. Much has been learned about dendritic cells in recent years: some types particularly 42-43 influence the development of Th1 cells and others Th2 cells . These dendritic populations can be identified on the basis of expression or absence of the adhesion molecule CD11c and also by the type of cytokines (such as IL-12) which they produce. The heterogeneity of dendritic cells is increasingly being recognised and it is now appreciated that the major function of some populations is to induce T cell tolerance, 44 rather than a productive immune response . As with all events in the immune system, a circular feedback system (so-called inter-cellular cross-talk) operates between dendritic cells and the T cells which they help stimulate (fig. 3). Thus, the cytokine products of dendritic cells influence the T cell populations which they generate and in turn, the cytokines produced by T cells 42 influence the type of dendritic cells which occupy that locale . A further population of cells, likely to be involved in antigen presentation, which express the macrophage scavenger receptor (CD163) has been identified by 45 immunohistochemistry in the central core of individual villi . The cytokine products of this population of macrophage-like cells, including secreted CD163, may play a role in 46 down-regulation of the local immune response . Cytokine environment of the mucosa Virtually all cells in the mucosa, including enterocytes, produce a wide range of cytokines and the profile of cytokines determines the net effect on the type of immune response elicited. It is presumed that a major, final determining influence is the type of cytokines produced by the local T helper populations. Since the principal default setting of the mucosal immune response is towards tolerance of encountered antigen, the cytokines which could determine tolerance have been investigated. The three cytokines which have received most interest for their potential involvement are IL-4, IL-10 and TGF-b. For some time it was considered that T cell tolerance in the mucosa was achieved by a predominant Th2 response to local antigens. Major products of Th2 cells include the cytokines IL-4 and IL-10. However, in some animal model experiments, it was shown that these cytokines are not required for tolerance induction. Moreover, in experimental oral tolerance, inhibition of IgE production is a characteristic feature: the reverse would 14 be predicted in an IL-4 dominant environment . Hence, it is now proposed that tolerance in the intestine may be achieved by a further T cell population, referred to as T 47 regulatory cells . The major cytokine products of these cells are IL-10 and transforming growth factor-beta (TGF-b). Although IL-10 is not essential in some models of oral tolerance, the importance of this cytokine in maintaining tolerance is emphasized by the spontaneous development 48 of colitis in mice when the gene for this cytokine is “knocked out” . Of great interest, 49 TGF-bcan reverse the colitis . It is also known that IL-10 may be required for the production of TGF-band that the latter cytokine inhibits the IL-12/interferon-gamma 50 (IFN-g) pathway, likely to play a central role in many inflammatory diseases . It is currently hypothesised that control of the mucosal immune system is maintained by regulatory T cells, but at present, other than studying their cytokine
MECHANISMS OF ORAL TOLERANCE 69 IEL Lamina propria M cell CD4 DC Cytokines of each cell type influence each other Epithelial lining Fig. 3. Interaction between CD4 + T cells and dendritic cells in lamina propria of the mucosa. DC = dendritic cell; IEL = intraepithelial lymphocyte. products, we do not have reliable, specific markers for these cells. It is probable that TGF-band IL-10 are major products of these cells. However, it should be emphasised, that even when a cytokine is shown not to be essential for experimental oral tolerance, this does not mean that in vivo, this cytokine has no role to play, since a level of redundancy is a common feature of the immune system. Mucosal immune tolerance and coeliac disease The preceding discussion of mucosal immune tolerance raises issues which may be pertinent to the pathogenesis of coeliac disease. Is the essential defect in coeliac disease a failure of the normal tolerance mechanisms, which allow gluten exposure but no mucosal damage in normal individuals? If so, might tolerance of gluten be restored and thereby permit CD patients to eat a normal diet? If this were possible, how might we go about achieving it? Obviously, these are major issues and it could be argued that restoring tolerance to gluten is a fanciful solution, perhaps unlikely ever to be achieved. Nonetheless, with the gathering pace of modern knowledge and technology, it is a goal which should at least be examined. Adolescent coeliac disease Some 30 years ago, one of the most frequent inquiries about the nature of CD, was whether gluten intolerance was permanent. Of course, the dogma now is that permanent
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Perspectives on Coeliac Disease Vol
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The AIC Meeting was held in the Aul
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Italian Coeliac Society, Via Picott
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Preface Coeliac disease (CD) is a u
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Contents Current understanding of t
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2 THE BASIS OF COELIAC DISEASE hapl
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4 THE BASIS OF COELIAC DISEASE 1 pr
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6 THE BASIS OF COELIAC DISEASE spre
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8 THE BASIS OF COELIAC DISEASE Ackn
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10 THE BASIS OF COELIAC DISEASE glu
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Catassi C, Fasano A, Corazza GR (ed
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T CELL RESPONSES TO GLUTEN PEPTIDES
Page 32 and 33: 18 A DOMINANT EPITOPE IN GLUTEN PEP
Page 42 and 43: 28 ROLE OF A-GLIADIN 31-49 PEPTIDE
Page 45 and 46: Catassi C, Fasano A, Corazza GR (ed
Page 47 and 48: COELIAC DISEASE IN THE SAHARAWI 33
Page 55: COELIAC DISEASE IN THE SAHARAWI 41
Page 58 and 59: 44 INFANT FEEDING PRACTICES AND COE
Page 66 and 67: Age (years) 52 INFANT FEEDING PRACT
Page 76 and 77: 62 MECHANISMS OF ORAL TOLERANCE the
Page 78 and 79: 64 MECHANISMS OF ORAL TOLERANCE pot
Page 80 and 81: 66 MECHANISMS OF ORAL TOLERANCE Epi
Page 84 and 85: 70 MECHANISMS OF ORAL TOLERANCE 51
Page 86 and 87: 72 MECHANISMS OF ORAL TOLERANCE 23.
Page 91 and 92: GENETICALLY DETOXIFIED GRAINS 77 to
Page 93 and 94: • • GENETICALLY DETOXIFIED GRAI
Page 95 and 96: GENETICALLY DETOXIFIED GRAINS 81 3.
Page 99 and 100: IMMUNOTHERAPY OF COELIAC DISEASE 85
Page 101 and 102: IMMUNOTHERAPY OF COELIAC DISEASE 87
Page 105 and 106: RECENT ADVANCES ON GLUTEN TOXICITY
Page 107 and 108: Index A Antiendomysium antibodies (
Page 109: INDEX 95 W Wheat, 7, 23, 27, 31, 53
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