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¹ Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany
² Paul-Ehrlich-Institute, 63225 Langen, Germany
³ Division of Molecular Immunology, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany
⁴ Institute for Infectious Diseases and Zoonoses, University of Munich, 80539 Munich, Germany

CORRESPONDENCE Reinhold Förster: Foerster.Reinhold{at}MH-Hannover.de

Mucosal vaccination via the respiratory tract can elicit protective immunity in animal infection models, but the underlying mechanisms are still poorly understood. We show that a single intranasal application of the replication-deficient modified vaccinia virus Ankara, which is widely used as a recombinant vaccination vector, results in prominent induction of bronchus-associated lymphoid tissue (BALT). Although initial peribronchiolar infiltrations, characterized by the presence of dendritic cells (DCs) and few lymphocytes, can be found 4 d after virus application, organized lymphoid structures with segregated B and T cell zones are first observed at day 8. After intratracheal application, in vitro–differentiated, antigen-loaded DCs rapidly migrate into preformed BALT and efficiently activate antigen-specific T cells, as revealed by two-photon microscopy. Furthermore, the lung-specific depletion of DCs in mice that express the diphtheria toxin receptor under the control of the CD11c promoter interferes with BALT maintenance. Collectively, these data identify BALT as tertiary lymphoid structures supporting the efficient priming of T cell responses directed against unrelated airborne antigens while crucially requiring DCs for its sustained presence.

Abbreviations used: AM, alveolar macrophage; BAL, bronchioalveolar lavage; BALT, bronchus-associated lymphoid tissue; brLN, bronchial LN; DT, diphtheria toxin; DTR, DT receptor; EGFP, enhanced GFP; i.n., intranasal; i.t., intratracheal; IU, infectious unit; MVA, modified vaccinia virus Ankara; SHG, second harmonics generation.

© 2009 Halle et al.
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