Abstract
BackgroundTh2 cell activation and T regulatory cell (Treg) deficiency are key features of allergy. This applies for asthma and rhinitis. However with a same atopic background, some patients will develop rhinitis and asthma, whereas others will display rhinitis only. Co-receptors are pivotal in determining the type of T cell activation, but their role in allergic asthma and rhinitis has not been explored. Our objective was to assess whether allergen-induced T cell activation differs from allergic rhinitis to allergic rhinitis with asthma, and explore the role of ICOS, CD28 and CTLA-4.MethodsT cell co-receptor and cytokine expressions were assessed by flow cytometry in PBMC from 18 house dust mite (HDM) allergic rhinitics (R), 18 HDM allergic rhinitics and asthmatics (AR), 13 non allergic asthmatics (A) and 20 controls, with or without anti-co-receptors antibodies.ResultsIn asthmatics (A+AR), a constitutive decrease of CTLA-4+ and of CD4+CD25+Foxp3+ cells was found, with an increase of IFN-γ+ cells. In allergic subjects (R + AR), allergen stimulation induced CD28 together with IL-4 and IL-13, and decreased the proportion of CTLA-4+, IL-10+ and CD4+CD25+Foxp3+ cells. Anti-ICOS and anti-CD28 antibodies blocked allergen-induced IL-4 and IL-13. IL-13 production also involved CTLA-4.ConclusionsT cell activation differs between allergic rhinitis and asthma. In asthma, a constitutive, co-receptor independent, Th1 activation and Treg deficiency is found. In allergic rhinitis, an allergen-induced Treg cell deficiency is seen, as well as an ICOS-, CD28- and CTLA-4-dependent Th2 activation. Allergic asthmatics display both characteristics.
Highlights
Th2 cell activation and T regulatory cell (Treg) deficiency are key features of allergy
We hypothesize since several years that T cell activation is different between both conditions and with others we previously described a Th1 activation in asthma that was absent in non asthmatic allergy in blood, induced sputum and broncho-alveolar lavages [10-12]
Allergen-induced T cell activation depends on signals delivered from antigen presenting cells (APCs) through the antigen-specific T cell receptor as well as additional co-stimulatory signals provided by engagement of socalled co-receptors on APCs and T cells [13]
Summary
Th2 cell activation and T regulatory cell (Treg) deficiency are key features of allergy. Co-receptors are pivotal in determining the type of T cell activation, but their role in allergic asthma and rhinitis has not been explored. The inflammatory response to common environmental allergens during allergy and asthma has been extensively studied in the past years, and has clearly determined the pivotal role of T cell activation, with a predominant Th2 cytokine production [2,3]. Major T cell co-receptors are CD28, inducible costimulatory molecule (ICOS) and cytotoxic T lymphocyte antigen (CTLA)-4. They belong to the immunoglobulin gene superfamily and display various kinetics of expression. ICOS was initially shown to selectively induce high levels of IL-10 and IL-4, but is able to stimulate both Th1 and Th2 cytokine production in vivo [14]
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