RRC ID 41336
Author Wu Q, Sun Y, Wang J, Lin X, Wang Y, Pegg LE, Fütterer A, Pfeffer K, Fu YX.
Title Signal via lymphotoxin-beta R on bone marrow stromal cells is required for an early checkpoint of NK cell development.
Journal J Immunol
Abstract NK cells play an important role in the immune system but the cellular and molecular requirements for their early development are poorly understood. Lymphotoxin-alpha (LTalpha)(-/-) and LTbetaR(-/-) mice show a severe systemic reduction of NK cells, which provides an excellent model to study NK cell development. In this study, we show that the bone marrow (BM) or fetal liver cells from LTalpha(-/-) or LTbetaR(-/-) mice efficiently develop into mature NK cells in the presence of stromal cells from wild-type mice but not from LTalpha(-/-) or LTbetaR(-/-) mice. Direct activation of LTbetaR-expressing BM stromal cells is shown to promote to early NK cell development in vitro. Furthermore, the blockade of the interaction between LT and LTbetaR in adult wild-type mice by administration of LTbetaR-Ig impairs the development of NK cells in vivo. Together, these results indicate that the signal via LTbetaR on BM stromal cells by membrane LT is an important pathway for early NK cell development.
Volume 166(3)
Pages 1684-9
Published 2001-2-1
DOI 10.4049/jimmunol.166.3.1684
PMID 11160211
MeSH Adoptive Transfer Animals Bone Marrow Cells / cytology Bone Marrow Cells / immunology* Bone Marrow Cells / metabolism Bone Marrow Transplantation Cell Differentiation / genetics Cell Differentiation / immunology Cell Line Cells, Cultured Hematopoietic Stem Cells / cytology* Hematopoietic Stem Cells / immunology* Hematopoietic Stem Cells / pathology Homeostasis / immunology Killer Cells, Natural / cytology* Killer Cells, Natural / immunology* Killer Cells, Natural / metabolism Killer Cells, Natural / pathology Lymphocyte Activation / genetics Lymphocyte Count Lymphoid Tissue / immunology Lymphoid Tissue / pathology Lymphopenia / genetics Lymphopenia / immunology Lymphopenia / therapy Lymphotoxin beta Receptor Lymphotoxin-alpha / genetics Lymphotoxin-alpha / metabolism* Lymphotoxin-beta Membrane Proteins / metabolism* Mice Mice, Inbred C57BL Mice, Knockout Receptors, Tumor Necrosis Factor / deficiency Receptors, Tumor Necrosis Factor / genetics Receptors, Tumor Necrosis Factor / physiology* Signal Transduction / genetics Signal Transduction / immunology* Stromal Cells / immunology Stromal Cells / metabolism T-Lymphocyte Subsets / pathology
IF 4.718
Times Cited 51
Human and Animal Cells