primary prevention of coeliac disease - Associazione Italiana ...

MECHANISMS OF ORAL TOLERANCE
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interposed between the lining epithelial cells and following uptake of antigen,
particulate antigen is processed and presented to local T helper cells. This in turn results
in a systemic immune response to the antigen.
As discussed earlier, in contrast to other food antigens, gluten appears to have an
unique capacity to stimulate a local T cell mediated immune response in CD patients,
leading to damage of the local mucosa. The chemical properties of gluten involved in
eliciting such a response are unknown, since no essential structural difference is
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thought to exist between self-antigens and foreign antigens .
Intraepithelial lymphocytes
Intraepithelial lymphocytes (IELs) are T cells located within the surface epithelium
of the mucosa. Despite intense research of these cells over the past two decades, their
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principal function remains enigmatic . The majority of IELs express the CD8
molecule and employ the abT cell receptor (TCR). It is well established that increased
numbers of IELs are found in certain intestinal inflammatory states such as coeliac
disease. Moreover, in coeliac disease the number of IELs expressing the gdTCR
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increases, with as many as 30% belonging to this phenotype . According to recent
evidence, IELs may include heterogeneous populations of T cells, natural killer T cells
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and also natural killer cells . It has been speculated that IELs play a role in oral
tolerance and there is some experimental evidence to support a role for gdT cells in
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tolerance induction .
Lamina propria T cells
The major population of lamina propria T cells express the CD4 molecule and
employ the abTCR. These T helper cells are thought to have initially encountered
mucosal antigen in organised lymphoid structures such as Peyer's patches and after
passage through the systemic circulation have specifically homed back to the intestine.
In this location, lamina propria T cells play a major role in orchestrating other cells of
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the immune system and act as conductors of this orchestra . These T cells possess a full
range of surface molecules to allow productive interaction with many other cell types.
Moreover, individual populations manufacture the variety of cytokines required to
influence B cell production of specific antibody isotypes, to induce specific populations
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of antigen presenting cells and to activate other populations of T cells . Thus,
regulation of immune events in the intestine is largely a function of these cells, and
hence maintenance of “oral tolerance” or mucosal immune homeostasis is likely to be
achieved by these cells.
Dendritic and other antigen presenting cells
The activation of intestinal T cells requires the presentation of antigen by local
populations of antigen presenting cells (APCs). This task may be performed by a
variety of APCs including dendritic cells, macrophages, B cells and, as discussed
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earlier, possibly by enterocytes . Populations of all these cell types have been
identified in the mucosal tissue. In individual situations, it is likely that the presentation
of antigen is principally performed by specific cell types. Dendritic cells, in particular,
may play a central role in presenting antigen and influencing the evolution of specific