Cutting edge: IL-7 regulates the peripheral pool of adult ROR gamma+ lymphoid tissue inducer cells.
During fetal life, CD4(+)CD3(-) lymphoid tissue inducer (LTi) cells are required for lymph node and Peyer's patch development in mice. In adult animals, CD4(+)CD3(-) cells are found in low numbers in lymphoid organs. Whether adult CD4(+)CD3(-) cells are LTi cells and are generated and maintained through cytokine signals has not been directly addressed. In this study we show that adult CD4(+)CD3(-) cells adoptively transferred into neonatal CXCR5(-/-) mice induced the formation of intestinal lymphoid tissues, demonstrating for the first time their bona fide LTi function. Increasing IL-7 availability in wild-type mice either by IL-7 transgene expression or treatment with IL-7/anti-IL-7 complexes increased adult LTi cell numbers through de novo generation from bone marrow cells and increased the survival and proliferation of LTi cells. Our observations demonstrate that adult CD4(+)lineage(-) cells are LTi cells and that the availability of IL-7 determines the size of the adult LTi cell pool.
Schmutz
Sandrine
S
Division of Developmental Immunology, Department of Biomedicine, University of Basel, Basel, Switzerland.
Bosco
Nabil
N
Chappaz
Stephane
S
Boyman
Onur
O
Acha-Orbea
Hans
H
Ceredig
Rhodri
R
Rolink
Antonius G
AG
Finke
Daniela
D
D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D005333:Fetus / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015851:Interleukin-7 / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D042583:Lymphangiogenesis / Q000235:genetics / Q000276:immunology*; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis* / Q000172:deficiency / Q000502:physiology; D011988:Receptors, Thyroid Hormone / Q000096:biosynthesis* / Q000172:deficiency / Q000502:physiology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
D017252:CD3 Complex; D015851:Interleukin-7; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; C539901:Rorc protein, mouse