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The role of peanut-specific T cell responses in children with peanut allergy and in children who are tolerant to peanuts
Project Code: T07041;
1. V. Turcanu, M. Winterbotham, P. Kelleher and G. Lack, Peanut-specific B and T cell Responses Are Correlated in Peanut Allergic but not in Non-allergic Individuals. Clin Exp Allergy, 38:1132-1139, 2008. DOI: 10.1111/j.1365-2222.2008.03016.x
2. Turcanu V, Stephens AC, Chan SMH, Rancé F, Lack G. IgE-mediated facilitated antigen presentation underlies higher immune responses in peanut allergy. Allergy 2010; 65: 1274–1281. DOI: 10.1111/j.1398-9995.2010.02367.x
3. Chan, S., V. Turcanu, V., Stephens, A.C., Lack, G., In Vitro Evidence For Different Routes Of Sensitization To Peanut In Children. The Journal of Allergy and Clinical Immunology
Volume 121, Issue 2, Supplement 1 , Page S214, February 2008 doi:10.1016/j.jaci.2007.12.799
4. Chan, S., Turcanu, V., Stephens, A., Fox, A., Grieve, A., Lack G. (2012) Cutaneous lymphocyte antigen and a4b7 T-lymphocyte responses are associated with peanut allergy and tolerance in children. Allergy, 67 (3): 336–342.
1. S.M.H. Chan, V. Turcanu, A.C. Stephens, G. Lack, In Vitro Evidence For Different Routes Of Sensitization To Peanut In Children J Allergy Clin Immunol 121: S214, 2008.
2. S. Hingley, G. Du Toit, G. Roberts, V. Turcanu, G. Lack, H. Fisher, and P. Lau, Peanut-specific IgG4 and its association with peanut allergy. J Allergy Clin Immunol 117: S33, 2006.
3. V. Turcanu, A.C. Stephens and G. Lack IgE-mediated facilitated antigen presentation augments immune responses to peanut antigens in allergic individuals compared with tolerant individuals - The annual meeting of the European Academy of Allergy, Asthma and Clinical Immunology, June 2006
4. V. Turcanu and G. Lack, Levels of peanut-specific precursor T cells reflect peanut allergy status. J Allergy Clin Immunol 115: S62, 2005.
Kings College London
Lack, G ; Turcanu, V
In both peanut allergic (PA) and tolerant to peanut (NA) children, peanut specific responses were found to be driven by memory Th cells and not by naïve T cells. The researchers could not find any obvious differences between the levels of suppressor cytokines produced in peanut-specific responses by peanut allergic (PA) and tolerant to peanut (NA) children. Therefore it seems very unlikely that suppressor cytokines are the cause of the differences between PA and NA states.
In the second stage of the study, the researchers findings confirmed that B cell responses to allergens (but not those to non-allergenic proteins) are ongoing responses that are closely linked with allergen –specific T cell responses, possibly through the positive feedback mechanism triggered by IgE-mediated facilitated antigen presentation (FAP).
In the third stage of the research, it was found that in peanut allergic (PA) children, the peanut-specific response is predominantly generated by skin-homing CLA+ memory T cells that have initially seen peanut antigens in the skin. Peanut-specific responses in children tolerant to peanut (NA) are generated by both skin-homing and gut-homing memory Th cells. It seems that these differences are specific for peanut responses as when carried out with a control food antigen (ovalbumin), no differences were seen between peanut allergic (PA) and tolerant to peanut (NA) children i.e. control responses showed no clear subset predominance of skin-homing or gut-homing memory Th cells.
This results are potentially very significant because they suggest that exposure to peanut allergen through the skin might be the major sensitising route and that interventions aimed at preventing peanut allergy should be focused on this route of exposure. It is hypothesised that skin exposure to peanuts, presumably through inflamed, eczematous skin may lead to peanut allergy development. New Agency funded research is looking into this further (T07060).
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