Induced bronchus-associated lymphoid tissue serves as a general priming site for T cells and is maintained by dendritic cells

被引:223
作者
Halle, Stephan [1 ]
Dujardin, Helene C. [1 ]
Bakocevic, Nadja [1 ]
Fleige, Henrike [1 ]
Danzer, Heike [1 ]
Willenzon, Stefanie [1 ]
Suezer, Yasemin [2 ]
Haemmerling, Guenter [3 ]
Garbi, Natalio [3 ]
Sutter, Gerd [4 ]
Worbs, Tim [1 ]
Foerster, Reinhold [1 ]
机构
[1] Hannover Med Sch, Inst Immunol, D-30625 Hannover, Germany
[2] Paul Ehrlich Inst, D-63225 Langen, Germany
[3] Deutsch Krebsforschungszentrum, Div Mol Immunol, D-69120 Heidelberg, Germany
[4] Univ Munich, Inst Infect Dis & Zoonoses, D-80539 Munich, Germany
关键词
VACCINIA VIRUS ANKARA; CUTTING EDGE; IN-VIVO; INDUCTION; VECTOR; BALT; LUNG; MICE; ACTIVATION; RESPONSES;
D O I
10.1084/jem.20091472
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:2593 / 2601
页数:9
相关论文
共 27 条
[1]   Vaccination with a Modified Vaccinia Virus Ankara-based vaccine protects mice from allergic sensitization [J].
Albrecht, Melanie ;
Suezer, Yasemin ;
Staib, Caroline ;
Sutter, Gerd ;
Vieths, Stefan ;
Reese, Gerald .
JOURNAL OF GENE MEDICINE, 2008, 10 (12) :1324-1333
[2]   GUT-ASSOCIATED AND BRONCHUS-ASSOCIATED LYMPHOID-TISSUE [J].
BIENENSTOCK, J ;
BEFUS, D .
AMERICAN JOURNAL OF ANATOMY, 1984, 170 (03) :437-445
[3]   Aerosol immunization with NYVAC and MVA vectored vaccines is safe, simple, and immunogenic [J].
Corbett, Max ;
Bogers, Willy M. ;
Heeney, Jonathan L. ;
Gerber, Stefan ;
Genin, Christian ;
Didierlaurent, Arnaud ;
Oostermeijer, Herman ;
Dubbes, Rob ;
Braskamp, Gerco ;
Lerondel, Stephanie ;
Gomez, Carmen E. ;
Esteban, Mariano ;
Wagner, Ralf ;
Kondova, Ivanella ;
Mooij, Petra ;
Balla-Jhagjhoorsingh, Sunita ;
Beenhakker, Niels ;
Koopman, Gerrit ;
van der Burg, Sjoerd ;
Kraehenbuhl, Jean-Pierre ;
Le Pape, Alain .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (06) :2046-2051
[4]   CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs [J].
Förster, R ;
Schubel, A ;
Breitfeld, D ;
Kremmer, E ;
Renner-Müller, I ;
Wolf, E ;
Lipp, M .
CELL, 1999, 99 (01) :23-33
[5]   Recombinant poxviruses as mucosal vaccine vectors [J].
Gherardi, MM ;
Esteban, M .
JOURNAL OF GENERAL VIROLOGY, 2005, 86 :2925-2936
[6]   Induction of tolerance to innocuous inhaled antigen relies on a CCR7-dependent dendritic cell-mediated antigen transport to the bronchial lymph node [J].
Hintzen, Gabriele ;
Ohl, Lars ;
del Rio, Maria-Luisa ;
Rodriguez-Barbosa, Jose-Ignacio ;
Pabst, Oliver ;
Kocks, Jessica R. ;
Krege, Janet ;
Hardtke, Svenja ;
Foerster, Reinhold .
JOURNAL OF IMMUNOLOGY, 2006, 177 (10) :7346-7354
[7]   A novel CD11c.DTR transgenic mouse for depletion of dendritic cells reveals their requirement for homeostatic proliferation of natural killer cells [J].
Hochweller, Kristin ;
Striegler, Joerg ;
Haemmerling, Guenter J. ;
Garbi, Natalio .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2008, 38 (10) :2776-2783
[8]   Cutting Edge: Mucosal Application of a Lyophilized Viral Vector Vaccine Confers Systemic and Protective Immunity toward Intracellular Pathogens [J].
Kastenmuller, Wolfgang ;
Gasteiger, Georg ;
Stross, Leon ;
Busch, Dirk H. ;
Drexler, Ingo .
JOURNAL OF IMMUNOLOGY, 2009, 182 (05) :2573-2577
[9]   Regulatory T cells interfere with the development of bronchus-associated lymphoid tissue [J].
Kocks, Jessica R. ;
Davalos-Misslitz, Ana Clara Marques ;
Hintzen, Gabriele ;
Ohl, Lars ;
Foerster, Reinhold .
JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (04) :723-734
[10]   Chemokine Receptor CCR7 Contributes to a Rapid and Efficient Clearance of Lytic Murine γ-Herpes Virus 68 from the Lung, Whereas Bronchus-Associated Lymphoid Tissue Harbors Virus during Latency [J].
Kocks, Jessica R. ;
Adler, Heiko ;
Danzer, Heike ;
Hoffmann, Katharina ;
Jonigk, Danny ;
Lehmann, Ulrich ;
Foerster, Reinhold .
JOURNAL OF IMMUNOLOGY, 2009, 182 (11) :6861-6869