Ex vivo development of functional human lymph node and bronchus-associated lymphoid tissue.
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 alphabeta and gammadelta 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.
Tirouvanziam
Rabindra
R
Institut d'Embryologie Cellulaire et Moléculaire du CNRS UPR 9064, Nogent-sur-Marne, France.
Khazaal
Ibrahim
I
N'Sondé
Victoire
V
Peyrat
Marie-Alix
MA
Lim
Annick
A
de Bentzmann
Sophie
S
Fournié
Jean Jacques
JJ
Bonneville
Marc
M
Péault
Bruno
B
D000022:Abortion, Spontaneous; D000818:Animals; D001980:Bronchi / Q000196:embryology / Q000276:immunology*; D004622:Embryo, Mammalian; D005314:Embryonic and Fetal Development; D005260:Female; D005333:Fetus; D005865:Gestational Age; D006801:Humans; D018928:Immunity, Mucosal; D008198:Lymph Nodes / Q000196:embryology / Q000276:immunology*; D008221:Lymphoid Tissue / Q000196:embryology / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D023421:Models, Animal; D009092:Mucous Membrane / Q000196:embryology / Q000276:immunology; D011247:Pregnancy; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D016511:Severe Combined Immunodeficiency / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014183:Transplantation, Heterologous / Q000276:immunology
D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta