Immunology of Asthma and Allergy

Professor Douglas Robinson, Group Leader

 

The Immunology of Asthma and Allergy Group are studying the biology of regulatory T cells in health and allergic diseases and the influence of treatments, including corticosteroids and conventional and peptide immunotherapy on these regulatory responses. Our group was set up as a link between Allergy and Clinical Immunology and the Leukocyte Biology Section (Head Professor Tim Williams) in 2002 with funding from the Wellcome Trust.

We have addressed the question of why everyone does not make a potentially harmful Th2 response to common allergens such as cat dander or grass pollen.  Regulatory T cells which actively suppress activation of harmful T cell responses have been defined in both mouse models and humans.  These include CD4+CD25+ T cells and IL-10-producing Tregs.  We have developed immunomagnetic separation techniques and in vitro culture assays to assess the potential function of these cells in prevention of allergic disease.  Our results demonstrate that CD4+CD25+ T cells from human blood can suppress Th2 responses to allergen, and that this process is less effective when cells from allergic volunteers are compared to those without allergic sensitisation.  This suggests that Th2 responses to allergens may normally be actively suppressed and that such suppression is overcome when patients develop allergic disease (these data were published in the Lancet: see Ling et al 2004).

 

We have collaborated with Professor Stephen Durham and Professor Barry Kay and Dr Mark Larché to investigate the ability of allergen immunotherapy with whole allergen extracts or peptides to induce regulatory T cells.  Our data suggests that there is no change in suppressive activity of CD4+CD25+ T cells with immunotherapy, but, in a collaboration with Professor David Wraith (University of Bristol), we have demonstrated increased suppressive activity of a CD4+CD25-IL-10 producing regulatory T cell subset in patients who have been treated with immunotherapy. Our current research involves investigating the actions of anti-allergic therapy on regulatory T cell acivity and further defining the effects of allergen exposure.

With Professor Barry Kay, we have developed human clinical models of acute and chronic asthma for the study of airway remodelling processes.

With Prof Fan Chung and the AARG we set up a protocol for evaluation of ‘difficult asthma’ within RBH and we now have a substantial clinical data base for research of this complex group of patients.