title: Contribution of CCR4 and CCR8 to antigen-specific T(H)2 cell trafficking in allergic pulmonary inflammation.
abstract: BACKGROUND
  Recruitment of antigen-specific T(H)2 cells into the lung is critical for the development of allergic airway inflammation. Although CCR4 and CCR8 are preferentially expressed on T(H)2 cells and CCR4, CCR8, and CXCR3 ligands are increased in asthma, the specific relative contribution of these receptors to antigen-specific T(H)2 cell trafficking into the allergic lung is not known.
  
  
  OBJECTIVE
  To determine the relative contribution of the chemokine receptors CCR4, CCR8, and CXCR3 to antigen-specific T(H)2 cell trafficking in a murine model of allergic pulmonary inflammation.
  
  
  METHODS
  We used adoptive transfer experiments to compare the trafficking of wild-type antigen-specific T(H)2 cells with antigen-specific T(H)2 cells deficient in CCR4, CCR8, or CXCR3.
  
  
  RESULTS
  CCR4-deficient antigen-specific T(H)2 cells failed to traffic efficiently into the lung and the airways. In contrast, CCR8-deficient antigen-specific T(H)2 cells accumulated in these sites. Trafficking of CXCR3-deficient antigen-specific T(H)2 cells and CCR4-deficient and CCR8-deficient antigen-specific T(H)1 cells were comparable to their wild-type counterparts. Approximately 60% of IL-4-producing antigen-specific T cells expressed CCR4. Disruption of CCR4-mediated antigen-specific T(H)2 cell trafficking decreased the levels of T(H)2-type cytokines in the airways and reduced airway eosinophilia and mucus production.
  
  
  CONCLUSIONS
  Our study demonstrates that CCR4 is required for the efficient entry of antigen-specific T(H)2 cells into the lung and the airways in a murine model of allergic pulmonary inflammation.
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Zamaneh
authors.initials: Z
authors.lastname: Mikhak
authors.forename: Mieko
authors.initials: M
authors.lastname: Fukui
authors.forename: Alireza
authors.initials: A
authors.lastname: Farsidjani
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Medoff
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Tager
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Luster
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011014:Pneumonia / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D054398:Receptors, CCR4 / Q000235:genetics / Q000276:immunology*; D054401:Receptors, CCR8 / Q000235:genetics / Q000276:immunology*; D054367:Receptors, CXCR3 / Q000235:genetics / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D000941:Antigens; C515355:Ccr4 protein, mouse; C489319:Ccr8 protein, mouse; C515188:Cxcr3 protein, mouse; D054398:Receptors, CCR4; D054401:Receptors, CCR8; D054367:Receptors, CXCR3