title: Multiple in vitro and in vivo regulatory effects of budesonide in CD4+ T lymphocyte subpopulations of allergic asthmatics.
abstract: BACKGROUND
  Increased activation and increased survival of T lymphocytes characterise bronchial asthma.
  
  
  OBJECTIVE
  In this study the effect of budesonide on T cell survival, on inducible co-stimulator T cells (ICOS), on Foxp3 and on IL-10 molecules in T lymphocyte sub-populations was assessed.
  
  
  METHODS
  Cell survival (by annexin V binding) and ICOS in total lymphocytes, in CD4+/CD25+ and in CD4+/CD25- and Foxp3 and IL-10 in CD4+/CD25+ and in CD4+/CD25-cells was evaluated, by cytofluorimetric analysis, in mild intermittent asthmatics (n = 19) and in controls (n = 15). Allergen induced T lymphocyte proliferation and the in vivo effects of budesonide in mild persistent asthmatics (n = 6) were also explored.
  
  
  RESULTS
  Foxp3 was reduced in CD4+/CD25- and in CD4+/CD25+ cells and ICOS was reduced in CD4+/CD25+ cells but it was increased in CD4+CD25-in asthmatics when compared to controls. In asthmatics, in vitro, budesonide was able to: 1) increase annexin V binding and to reduce ICOS in total lymphocytes; 2) increase annexin V binding and Foxp3 and to reduce ICOS in CD4+/CD25- cells; 3) reduce annexin V binding and to increase IL-10 and ICOS in CD4+/CD25+ cells; 4) reduce cell allergen induced proliferation. In vivo, budesonide increased ICOS in CD4+/CD25+ while it increased Foxp3 and IL-10 in CD4+/CD25+ and in CD4+/CD25- cells.
  
  
  CONCLUSIONS
  Budesonide modulates T cell survival, ICOS, Foxp3 and IL-10 molecules differently in T lymphocyte sub-populations. The findings provided shed light on new mechanisms by which corticosteroids, drugs widely used for the clinical management of bronchial asthma, control T lymphocyte activation.
authors.affiliation: Istituto di Biomedicina e Immunologia Molecolare, Unità di Immunopatologia e Farmacologia Clinica e Sperimentale dell'Apparato Respiratorio, Consiglio Nazionale delle Ricerche, Palermo, Italy. pace@ibim.cnr.it
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pace
authors.forename: Caterina
authors.initials: C
authors.lastname: Di Sano
authors.forename: Stefania
authors.initials: S
authors.lastname: La Grutta
authors.forename: Maria
authors.initials: M
authors.lastname: Ferraro
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Albeggiani
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Liotta
authors.forename: Serena
authors.initials: S
authors.lastname: Di Vincenzo
authors.forename: Carina Gabriela
authors.initials: CG
authors.lastname: Uasuf
authors.forename: Jean
authors.initials: J
authors.lastname: Bousquet
authors.forename: Mark
authors.initials: M
authors.lastname: Gjomarkaj
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D001993:Bronchodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019819:Budesonide / Q000494:pharmacology* / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
chemical_list: D001993:Bronchodilator Agents; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D060889:Inducible T-Cell Co-Stimulator Protein; D016753:Interleukin-10; D019819:Budesonide