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Identification of key chemokine-chemokine receptor interactions that control the memory Th2 cells in allergic asthma

Objective

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.

Field of science

  • /social sciences/sociology/social problems/migration
  • /medical and health sciences/clinical medicine/pneumology/asthma

Call for proposal

FP7-PEOPLE-2007-4-2-IIF
See other projects for this call

Funding Scheme

MC-IIF - International Incoming Fellowships (IIF)

Coordinator

MEDIZINISCHE UNIVERSITAET WIEN
Address
Spitalgasse 23
1090 Wien
Austria
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 227 092,62
Administrative Contact
Michelle Epstein (Dr.)