title: Enhanced allergen-induced airway inflammation in paucity of lymph node T cell (plt) mutant mice.
abstract: BACKGROUND
  Dendritic cells and lymphocytes play a central role in allergic asthma. Chemokines for these cells include the CCR7 agonists secondary lymphoid chemokine/CCL21 and EBV-induced lymphoid chemokine/CCL19, but their role in allergic asthma is poorly understood.
  
  
  OBJECTIVE
  We sought to determine the effects of abrogation of lymphoid tissue expression of CCR7 agonists on allergic airway responses.
  
  
  METHODS
  Paucity of lymphocyte T cell (plt) mutant mice, deficient in EBV-induced lymphoid chemokine/CCL19 and the lymphoid form of secondary lymphoid chemokine/CCL21, were evaluated in an established ovalbumin (OVA)-induced asthma model (plt-OVA group) and compared with similarly immunized +/+ BALB/c mice (+/+OVA group).
  
  
  RESULTS
  APTI responses to methacholine increased similarly in OVA-challenged plt and +/+ mice. However, airway inflammation was strikingly enhanced in plt-OVA mutants over +/+OVA mice and included increased numbers of eosinophils, CD4 and B cells, neutrophils, and total leukocytes in bronchoalveolar lavage fluid and inflammatory cell cuffing around pulmonary arterioles. Enhanced airway inflammation was accompanied by an increase in lung T(H)2 activity, with increased levels of IL-4 and monocyte-derived chemoattractant/CCL22.
  
  
  CONCLUSIONS
  Induction of allergic asthma in mutant mice with impaired CCR7 responses results in characteristics that resemble severe asthma in human subjects, including severe bronchial lymphocytosis, eosinophilia, and neutrophilia, but not in enhancement in airway hyperreactivity.
  
  
  CONCLUSIONS
  Disruption of chemokines responsible for trafficking of antigen-processing cells and lymphocytes to the draining lymph nodes might lead to enhanced allergic airway responses.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of Virginia School of Medicine, Charlottesville, VA 22901, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Grinnan
authors.forename: Sun-Sang
authors.initials: SS
authors.lastname: Sung
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Dougherty
authors.forename: Amy Ryce
authors.initials: AR
authors.lastname: Knowles
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Allen
authors.forename: Charles E
authors.initials: CE
authors.lastname: Rose
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakano
authors.forename: Michael D
authors.initials: MD
authors.lastname: Gunn
authors.forename: Shu Man
authors.initials: SM
authors.lastname: Fu
authors.forename: C Edward
authors.initials: CE
authors.lastname: Rose
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001160:Arterioles / Q000276:immunology; D001249:Asthma / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D001980:Bronchi; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054422:Chemokine CCL22; D019742:Chemokines, CC / Q000096:biosynthesis; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D005260:Female; D007249:Inflammation / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis; D007958:Leukocyte Count; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000276:immunology; D012137:Respiratory System / Q000098:blood supply / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000485:Allergens; C515460:CCL19 protein, human; C515478:CCL21 protein, human; C515482:CCL22 protein, human; C515370:CCR7 protein, human; C515461:Ccl19 protein, mouse; C515479:Ccl21c protein, mouse; C515483:Ccl22 protein, mouse; C515371:Ccr7 protein, mouse; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054422:Chemokine CCL22; D019742:Chemokines, CC; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D015847:Interleukin-4; D010047:Ovalbumin