Obiettivo Allergic asthma is a disease of airway inflammation caused by an allergic reaction to an antigen. Pathogenic CD4+ T helper type 2 (Th2) cells in lungs are involved in the initiation and perpetuation of the allergic response in airways of asthmatics and animals. Mouse models generated by systemic immunization and respiratory tract exposure with inhaled antigen or by adoptive transfer of effector Th2 cells into naive mice develop eosinophilic inflammation, mucus hypersecretion, and airway hyperreactivity. To mimic disease in asthmatics, we developed a relapsing-remitting mouse model, in we investigate mice during remission and secondary antigen lung challenge induced relapses. Recovered mice are characterized by the presence of Th2 memory lymphocytes in lungs for their lifetime. Exposure of recuperated mice to inhaled allergen reactivates these lung CD4+ Th2 memory cells, consequently initiating disease relapse. The factors governing the survival and retention of CD4+ Th2 cells in the lungs are unknown. One possibility is that memory CD4+ Th2 cells are retained in the lungs by chemokine- chemokine receptor (CKR) interactions. The objective of this project is to identify key chemokine-CKR interactions that control the migration of Th2 cells. We propose specifically, 1) to determine CKR expression on resting CD4+ T cells in the lungs during remission and correlate phenotype with effector function; 2) to identify the critical CKR expression on Th2 cells allowing them to immigrate from the lung during antigen exposure; and 3) to define antigen-specific Th2 cells using a novel transgenic adoptive transfer system. Discovering a reliable phenotype that distinguishes memory Th2 cells in the lungs would allow for their isolation and characterization and potentially lead to new approaches to prevent disease relapses and progression of allergic asthma. Campo scientifico medical and health sciencesclinical medicinepneumologyasthmamedical and health sciencesbasic medicineimmunologyimmunisation Parole chiave chemokine chemokine receptor interactions mice Programma(i) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) PEOPLE-2007-4-2.IIF - Marie Curie Action: "International Incoming Fellowships" Invito a presentare proposte FP7-PEOPLE-2007-4-2-IIF Vedi altri progetti per questo bando Meccanismo di finanziamento MC-IIF - International Incoming Fellowships (IIF) Coordinatore MEDIZINISCHE UNIVERSITAET WIEN Contributo UE € 227 092,62 Indirizzo SPITALGASSE 23 1090 Wien Austria Mostra sulla mappa Regione Ostösterreich Wien Wien Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Michelle Epstein (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato