Fibroblastic reticular cells in lymph nodes regulate the homeostasis of naive T cells.
Interleukin 7 is essential for the survival of naive T lymphocytes. Despite its importance, its cellular source in the periphery remains poorly defined. Here we report a critical function for lymph node access in T cell homeostasis and identify T zone fibroblastic reticular cells in these organs as the main source of interleukin 7. In vitro, T zone fibroblastic reticular cells were able to prevent the death of naive T lymphocytes but not of B lymphocytes by secreting interleukin 7 and the CCR7 ligand CCL19. Using gene-targeted mice, we demonstrate a nonredundant function for CCL19 in T cell homeostasis. Our data suggest that lymph nodes and T zone fibroblastic reticular cells have a key function in naive CD4(+) and CD8(+) T cell homeostasis by providing a limited reservoir of survival factors.
Link
Alexander
A
Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland.
Vogt
Tobias K
TK
Favre
Stéphanie
S
Britschgi
Mirjam R
MR
Acha-Orbea
Hans
H
Hinz
Boris
B
Cyster
Jason G
JG
Luther
Sanjiv A
SA
D019264:Adoptive Transfer; D000818:Animals; D002470:Cell Survival; D054415:Chemokine CCL19 / Q000276:immunology / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006706:Homeostasis / Q000276:immunology*; D017403:In Situ Hybridization; D015851:Interleukin-7 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology
D054415:Chemokine CCL19; D015851:Interleukin-7; D012333:RNA, Messenger