Enhanced allergen-induced airway inflammation in paucity of lymph node T cell (plt) mutant mice.
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.
Grinnan
Dan
D
Division of Pulmonary and Critical Care Medicine, University of Virginia School of Medicine, Charlottesville, VA 22901, USA.
Sung
Sun-Sang
SS
Dougherty
Joseph A
JA
Knowles
Amy Ryce
AR
Allen
Matthew B
MB
Rose
Charles E
CE
Nakano
Hideki
H
Gunn
Michael D
MD
Fu
Shu Man
SM
Rose
C Edward
CE
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
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