Type I food allergies are adverse reactions to food, mediated by immunoglobulin E (1gB) antibody, generated by the gut immune system towards food allergens. There is no known therapy at this time. The aim ofmy work was to dissect the role of dendritic cell-T cell interaction in the development of food allergy. Previous work showed that T cell-mediated apoptosis of dendritic cells (DCs) was impaired in a mouse model of food allergy but the biological relevance of this event is undetermined. T cell-mediated apoptosis was investigated in two mouse strains, with C3H1HeJ showing higher degree of susceptibility than Balb/c mice. In parallel, I aimed to compare the susceptibility of intestinal (Peyer's patch)- and systemic (spleen)-derived DC to T cell-mediated apoptosis in physiological condition (i.e non-sensitised). The latter study showed greater susceptibility of gut Peyer's Patch-derived DC (PP-DC) to antigen-specific T cell-mediated cell death (apoptosis) than spleen-derived DC. Also, similar levels of T cell-mediated apoptosis of DC were observed, irrespective of mouse strain, suggesting increased resistance to T cell-mediated apoptosis alone is not sufficient in triggering full 19B-mediated allergic reactions. However, significant alteration was observed in studies of DC capacity to secrete lymphokine Interleukin-12 (IL-12), which promotes T-helper 1 (Thl) responses. Interleukin-4 (IL-4)-mediated production of IL-12 was impaired in PP-DC of sensitised C3H1HeJ mice but not splenic, non-sensitised or in DC derived from Balb/c mice. This event was not dependent on IL-4 receptor availability upon DC but was linked to reciprocal control ofSTAT-6 and STAT-4 pathways leading IL-12 production by DC. My data indicates that the development of food allergy is linked to the simultaneous failure of at least two different immuno-regulatory mechanisms. A possible hypothesis from this suggests that restoring levels ofIL-12 in the gut may be a novel and effective strategy for food allergy therapy.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:502366 |
| Date | January 2008 |
| Creators | Temblay, Jeffrey Nann |
| Publisher | University of East Anglia |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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