Ectopic lymphoid-organ development occurs through interleukin 7-mediated enhanced survival of lymphoid-tissue-inducer cells.
Development of Peyer's patches and lymph nodes requires the interaction between CD4+ CD3- IL-7Ralpha+ lymphoid-tissue inducer (LTi) and VCAM-1+ organizer cells. Here we showed that by promoting their survival, enhanced expression of interleukin-7 (IL-7) in transgenic mice resulted in accumulation of LTi cells. With increased IL-7 availability, de novo formation of VCAM-1+ Peyer's patch anlagen occurred along the entire fetal gut resulting in a 5-fold increase in Peyer's patch numbers. IL-7 overexpression also led to formation of multiple organized ectopic lymph nodes and cecal patches. After immunization, ectopic lymph nodes developed normal T cell-dependent B cell responses and germinal centers. Mice overexpressing IL-7 but lacking either RORgamma, a factor required for LTi cell generation, or lymphotoxin alpha1beta2 had neither Peyer's patches nor ectopic lymph nodes. Therefore, by controlling LTi cell numbers, IL-7 can regulate the formation of both normal and ectopic lymphoid organs.
Meier
Dominik
D
Division of Developmental Immunology, Center for Biomedicine, Department of Clinical and Biological Sciences (DKBW), University of Basel, CH-4058 Basel, Switzerland.
Bornmann
Caroline
C
Chappaz
Stephane
S
Schmutz
Sandrine
S
Otten
Luc A
LA
Ceredig
Rhodri
R
Acha-Orbea
Hans
H
Finke
Daniela
D
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D002470:Cell Survival; D002478:Cells, Cultured; D005333:Fetus / Q000378:metabolism; D005786:Gene Expression Regulation; D015851:Interleukin-7 / Q000235:genetics / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D015851:Interleukin-7; D019010:Vascular Cell Adhesion Molecule-1