title: Differences in allergen-induced T cell activation between allergic asthma and rhinitis: Role of CD28, ICOS and CTLA-4.
abstract: BACKGROUND
  Th2 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.
  
  
  METHODS
  T 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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  T 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.
authors.affiliation: INSERM UMR915, Nantes, F-44000 France. botturikarine@yahoo.fr
authors.forename: Karine
authors.initials: K
authors.lastname: Botturi
authors.forename: Yannick
authors.initials: Y
authors.lastname: Lacoeuille
authors.forename: Arnaud
authors.initials: A
authors.lastname: Cavaillès
authors.forename: Daniel
authors.initials: D
authors.lastname: Vervloet
authors.forename: Antoine
authors.initials: A
authors.lastname: Magnan
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism*; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D001249:Asthma / Q000175:diagnosis / Q000276:immunology*; D018106:CD28 Antigens / Q000378:metabolism*; D060908:CTLA-4 Antigen; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006967:Hypersensitivity / Q000175:diagnosis / Q000276:immunology*; D060889:Inducible T-Cell Co-Stimulator Protein; D007428:Intradermal Tests; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012221:Rhinitis, Allergic, Perennial / Q000175:diagnosis / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D015703:Antigens, CD; D039741:Antigens, Dermatophagoides; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein