The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.20061424
The Journal of Experimental Medicine, Vol. 204, No. 4, 723-734
The Rockefeller University Press, 0022-1007 $30.00
© Kocks et al.
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ARTICLE

 Regulatory T cells interfere with the development of bronchus-associated lymphoid tissue

Jessica R. Kocks, Ana Clara Marques Davalos-Misslitz, Gabriele Hintzen, Lars Ohl, and Reinhold Förster

Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany

CORRESPONDENCE Reinhold Förster: foerster.reinhold{at}mh-hannover.de

Presence and extent of bronchus-associated lymphoid tissue (BALT) is subject to considerable variations between species and is only occasionally observed in lungs of mice. Here we demonstrate that mice deficient for the chemokine receptor CCR7 regularly develop highly organized BALT. These structures were not present at birth but were detectable from day 5 onwards. Analyzing CCR7–/–/wild-type bone marrow chimeras, we demonstrate that the development of BALT is caused by alterations of the hematopoietic system in CCR7-deficient mice. These observations together with the finding that CCR7-deficient mice posses dramatically reduced numbers of regulatory T cells (T reg cells) in the lung-draining bronchial lymph node suggest that BALT formation might be caused by disabled in situ function of T reg cells. Indeed, although adoptive transfer of wild-type T reg cells to CCR7-deficient recipients resulted in a profound reduction of BALT formation, neither naive wild-type T cells nor T reg cells from CCR7–/– donors impair BALT generation. Furthermore, we provide evidence that CCR7-deficient T reg cells, although strongly impaired in homing to peripheral lymph nodes, are fully effective in vitro. Thus our data reveal a CCR7-dependent homing of T reg cells to peripheral lymph nodes in conjunction with a role for these cells in controlling BALT formation.

Abbreviations used: BALT, bronchus-associated lymphoid tissue; brLN, bronchial LN; HEV, high endothelial venules; LT{alpha}, lymphotoxin {alpha}; LTIC, lymphoid tissue inducing cell; PP, Peyer's patches; SPF, specific pathogen–free; VCAM, vascular cell adhesion molecule.


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