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RESEARCH PRODUCT
Multiple in vitro and in vivo regulatory effects of budesonide in CD4+ T lymphocyte subpopulations of allergic asthmatics.
Jean BousquetCarina Gabriela UasufCaterina Di SanoGiuseppe AlbeggianiMaria FerraroGiuseppe LiottaSerena Di VincenzoStefania La GruttaMark GjomarkajElisabetta Pacesubject
BudesonideCD4-Positive T-LymphocytesMalePulmonologylcsh:Medicineimmune system diseasesT-Lymphocyte SubsetsMolecular Cell Biologylcsh:ScienceBudesonidecigarette smoke airway epithelial cells reactive oxygen species.MultidisciplinaryT CellsAllergy and HypersensitivityClinical Pharmacologyhemic and immune systemsForkhead Transcription Factorsrespiratory systemMiddle AgedFlow CytometryBronchodilator AgentsInterleukin-10Interleukin 10MedicineFemalemedicine.drugResearch ArticleAdultDrugs and DevicesAdolescentCell SurvivalImmune CellsImmunologychemical and pharmacologic phenomenaInducible T-Cell Co-Stimulator ProteinImmunomodulationIn vivomedicineHumansInducible T-Cell Co-Stimulator ProteinBiologyAsthmaCell Proliferationbusiness.industrylcsh:RT lymphocytemedicine.diseaseIn vitroAsthmarespiratory tract diseasesApoptosisImmunologylcsh:QClinical ImmunologybusinessCytometrydescription
Abstract BACKGROUND: Increased activation and increased survival of T lymphocytes characterise bronchial asthma. OBJECTIVES: 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2012-05-16 | PloS one |