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Blood, 1 April 2002, Vol. 99, No. 7, pp. 2483-2489
IMMUNOBIOLOGY
Ex vivo development of functional human lymph node and
bronchus-associated lymphoid tissue
Rabindra Tirouvanziam,
Ibrahim Khazaal,
Victoire N'Sondé,
Marie-Alix Peyrat,
Annick Lim,
Sophie de Bentzmann,
Jean
Jacques Fournié,
Marc Bonneville, and
Bruno Péault
From the Institut d'Embryologie Cellulaire et
Moléculaire du CNRS UPR 9064, Nogent-sur-Marne and INSERM U506,
Villejuif; INSERM U463, Nantes; INSERM U277, Paris; INSERM U514, Reims;
and INSERM U395, Toulouse, France.
We introduce a novel in vivo model of human mucosal immunity, based
on the implantation of human fetal bronchial mucosa and autologous
peribronchial lymph node (PLN) in the severe combined immunodeficiency
(SCID) mouse. In the SCID host, human fetal bronchi implanted alone
retain macrophages and mast cells but lose T cells. In contrast, fetal
bronchi co-implanted with PLN contain, in addition to macrophages and
mast cells, numerous T cells and B cells, often clustered in
intramucosal bronchus-associated lymphoid tissue (BALT).
Functionally, bronchus-PLN cografts are able to mount robust  
and   T-cell-mediated immune responses to Pseudomonas aeruginosa and 3,4-epoxy-3-methyl-1-butyl-diphosphate challenges. No other autologous lymphoid organ (bone marrow, thymus, liver) allows
for BALT development in co-implanted bronchi, which suggests special
ontogenetic and functional relations between extramucosal PLN and
intramucosal BALT. Overall, the bronchus-PLN cograft appears as a
promising model for human bronchial immune development and function.
Our study is the first to document long-term ex vivo maintenance of
functional human lymph nodes as native appendices to mucosal tissue.
Our results, therefore, suggest a simple strategy for developing
similar experimental models of human immune function in other mucosae.
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