International Immunology Advance Access originally published online on May 19, 2007
International Immunology 2007 19(6):775-784; doi:10.1093/intimm/dxm046
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Lack of lymphoid chemokines CCL19 and CCL21 enhances allergic airway inflammation in mice
1 Department of Environmental Medicine, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan
2 Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305-5176, USA
3 Department of Medicine, Kagoshima Seikyo Hospital, 5-20-10 Taniyama Chuo, Kagoshima 891-0141, Japan
4 Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
5 Department of Immunology, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan
6 Present address: Department of Pathology, Stanford University School of Medicine, CCSR 3250, 269 Campus Drive, Stanford, CA 94305-5176, USA
Correspondence to: B. Xu; E-mail: xubaohui{at}gmail.com
Lymphoid chemokines CCL19 and CCL21 are crucial for the recruitment of circulating naive T cells into lymph nodes. However, it is not completely known how they contribute to the development of allergic diseases. To determine whether the lack of CCL19 and CCL21 affects allergic airway inflammation, CCL19- and CCL21-deficient [paucity of lymph node T cells (plt/plt)] and wild-type (WT) mice were immunized intra-peritoneally and then challenged intra-nasally with chicken ovalbumin (OVA). Plt/plt mice developed more severe allergic airway inflammation characterized by increased eosinophils and lymphocytes in bronchoalveolar lavage (BAL) and profound inflammation in peribronchiolar and perivascular regions than did WT mice. CD4+ 
4 integrin+ and CD4+ ß7 integrin+ T cells were significantly increased in the BAL of OVA-immunized and OVA-challenged (OVA/OVA) plt/plt mice compared with OVA/OVA WT mice. Moreover, there were higher levels of IL-4 and IL-13 mRNAs and lower levels of IL-2 and IFN-
mRNAs in inflamed lungs of OVA/OVA plt/plt mice compared with OVA/OVA WT mice. Plt/plt mice produced higher levels of total and OVA-specific IgE antibody. Thus, our results suggest that lack of lymphoid chemokines CCL19 and CCL21 enhances allergic airway inflammation by modulating the recruitment of CD4+ T cells into the lung, the balance between Th1 and Th2 cytokines and the IgE production.
Keywords: airway hypersensitivity, adhesion molecule, chicken ovalbumin, cytokines, IgE
Transmitting editor: K. Okumura
Received 2 January 2007, accepted 22 March 2007.