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Priming of the immune response to Respiratory Syncytial Virus takes place in the lung in CCR7−/− mice
Author(s) -
Kallal Lara E,
Lukacs Nicholas W
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.665.11
Subject(s) - c c chemokine receptor type 7 , immunology , immune system , cd11c , antigen , chemokine , biology , priming (agriculture) , chemokine receptor , biochemistry , botany , germination , gene , phenotype
Chemokine receptor CCR7 is expressed on naïve T cells and is responsible for their trafficking into secondary lymphoid tissue to sample antigen. Conversely, CCR7 is upregulated on dendritic cells (DCs) upon antigen uptake and activation, permitting maturation and migration of DCs to the lymph nodes to prime T cell responses. We sought to investigate the role of DCs and T cells deficient in CCR7 during a primary pulmonary viral infection caused by Respiratory Syncytial Virus, a negative strand RNA virus that can cause severe complications in infants and immunocompromised individuals. We found that CCR7−/− mice had significantly elevated numbers of CD69+ CD4+ and CD8+ T cells in the lung. Consistent with this, expression of the Th2 cytokines IL‐4 and IL‐13, as well as the Th1 cytokine, IFNg, was upregulated in CCR7−/− mice. When we assayed for DC recruitment, we found significantly higher numbers of CD11b+CD11c+ cells in the lungs of CCR7−/− mice. Upon histological evaluation, the airways of CCR7−/− mice exhibited considerable mucus accumulation in the airways compared to WT. In accord with this, RT‐PCR for the mucus inducing genes, muc and gob5a, were highly upregulated in CCR7−/− mice. In the lymph node, however, total cellularity was decreased, suggesting that the immune response to RSV may be mediated locally in the lung by DCs and T cells that are unable to migrate properly in the absence of CCR7.