title: Expansion of CD4(+) CD25(+) and CD25(-) T-Bet, GATA-3, Foxp3 and RORγt cells in allergic inflammation, local lung distribution and chemokine gene expression.
abstract: Allergic asthma is associated with airway eosinophilia, which is regulated by different T-effector cells. T cells express transcription factors T-bet, GATA-3, RORγt and Foxp3, representing Th1, Th2, Th17 and Treg cells respectively. No study has directly determined the relative presence of each of these T cell subsets concomitantly in a model of allergic airway inflammation. In this study we determined the degree of expansion of these T cell subsets, in the lungs of allergen challenged mice. Cell proliferation was determined by incorporation of 5-bromo-2'-deoxyuridine (BrdU) together with 7-aminoactnomycin (7-AAD). The immunohistochemical localisation of T cells in the lung microenvironments was also quantified. Local expression of cytokines, chemokines and receptor genes was measured using real-time RT-PCR array analysis in tissue sections isolated by laser microdissection and pressure catapulting technology. Allergen exposure increased the numbers of T-bet(+), GATA-3(+), RORγt(+) and Foxp3(+) cells in CD4(+)CD25(+) and CD4(+)CD25(-) T cells, with the greatest expansion of GATA-3(+) cells. The majority of CD4(+)CD25(+) T-bet(+), GATA-3(+), RORγt(+) and Foxp3(+) cells had incorporated BrdU and underwent proliferation during allergen exposure. Allergen exposure led to the accumulation of T-bet(+), GATA-3(+) and Foxp3(+) cells in peribronchial and alveolar tissue, GATA-3(+) and Foxp3(+) cells in perivascular tissue, and RORγt(+) cells in alveolar tissue. A total of 28 cytokines, chemokines and receptor genes were altered more than 3 fold upon allergen exposure, with expression of half of the genes claimed in all three microenvironments. Our study shows that allergen exposure affects all T effector cells in lung, with a dominant of Th2 cells, but with different local cell distribution, probably due to a distinguished local inflammatory milieu.
authors.affiliation: Department of Internal Medicine, Krefting Research Centre, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: You
authors.initials: Y
authors.lastname: Lu
authors.forename: Carina
authors.initials: C
authors.lastname: Malmhäll
authors.forename: Margareta
authors.initials: M
authors.lastname: Sjöstrand
authors.forename: Madeleine
authors.initials: M
authors.lastname: Rådinger
authors.forename: Serena E
authors.initials: SE
authors.lastname: O'Neil
authors.forename: Jan
authors.initials: J
authors.lastname: Lötvall
authors.forename: Apostolos
authors.initials: A
authors.lastname: Bossios
mesh_terms: D000485:Allergens / Q000633:toxicity*; D000818:Animals; D015153:Blotting, Western; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000235:genetics* / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced* / Q000276:immunology* / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000098815:T-bet Transcription Factor
chemical_list: D000485:Allergens; D015704:CD4 Antigens; D018925:Chemokines; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D050990:GATA3 Transcription Factor; D053645:Interleukin-2 Receptor alpha Subunit; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor