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Listen to this siteMonday 27 November 2006
This research project will further our understanding of T cell responses in tolerant individuals thereby devising immunomodulatory strategies to normalise T cell responses in future therapies.
Study Duration : April 2004 to March 2008
Contractor : King's College London
Peanut allergy is a severe, potentially life-threatening condition in children characterised by severe anaphylactic reactions triggered by even minute quantities of peanut allergen. It remains unclear why some children develop peanut allergy, others tolerate peanut their whole lives and other children outgrow their peanut allergy to subsequently develop tolerance. It is equally unclear why some children have evidence of specific IgE to peanut or a positive skin prick test to peanut and nevertheless eat large quantities of peanut without ill effect. In previous FSA-funded work, clinical and immunological observations relating to the different states of peanut allergy and tolerance have been made. This study will enable us to further understand T cell responses in the pathogenesis of food allergy by understanding the mechanisms that underlie T cell responses in tolerant individuals and devise new immunomodulatory strategies that could allow us to normalise T cell responses in future therapies.
In the first stage of this study, a recently developed method will be used to explain the differences in the mechanism of T cell responses in children with peanut allergy (PA), tolerant children (NA) and outgrowers (OG). In particular, differences in memory versus na
ve T cell responses and allergy specific T cell precursor frequency will be investigated. Also to be investigated is the role of suppressor T cells and whether IgE mediated facilitated antigen presentation (FAP) can explain the observed differences.
In the second stage of the study, observations on T cell responses will be extended to include children with peanut sensitisation who are able to tolerate peanut. This would enable clinical differences between peanut allergic and peanut sensitised individuals to be established.
The third stage of the study will investigate the site (via the skin or gut) where sensitization to peanut has occurred in peanut allergic individuals.
Memory T cells express �homing receptors� on their surface that assist the circulation of the T cell through lymph nodes, lymphatics and the blood before returning to the tissue where the T cell is most likely to encounter the allergen again. The researchers will investigate two specific homing receptors - the Cutaneous Lymphocyte-associated antigen (CLA) - a skin homing receptor, the expression of which implies sensitization in the skin and α4β7 integrin - a gut homing receptor, the expression of which implies sensitization in the gut. These studies will compare the proliferative T cell responses to peanut in peanut allergic children amongst the CLA-expressing (skin homing) and α4β7 integrin-expressing (gut homing) T cell populations.
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