A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function.
Dendritic cells are rare haematopoietic cells that reside in a number of organs and tissues. By capturing, processing and presenting antigens to T cells, dendritic cells are essential for immune surveillance and the regulation of specific immunity. Several members of the tumour necrosis factor receptor (TNFR) superfamily are integral to the regulation of the immune response. These structurally related proteins modulate cellular functions ranging from proliferation and differentiation to inflammation and cell survival or deaths. The functional activity of dendritic cells is greatly increased by signalling through the TNFR family member CD40. Here we report the characterization of RANK (for receptor activator of NF-kappaB), a new member of the TNFR family derived from dendritic cells, and the isolation of a RANK ligand (RANKL) by direct expression screening. RANKL augments the ability of dendritic cells to stimulate naive T-cell proliferation in a mixed lymphocyte reaction, and increases the survival of RANK+ T cells generated with interleukin-4 and transforming growth factor (TGF)-beta. Thus RANK and RANKL seem to be important regulators of interactions between T cells and dendritic cells.
Anderson
D M
DM
Department of Molecular Biology, Immunex Corporation, Seattle, Washington 98101, USA. andersond@immunex.com
Maraskovsky
E
E
Billingsley
W L
WL
Dougall
W C
WC
Tometsko
M E
ME
Roux
E R
ER
Teepe
M C
MC
DuBose
R F
RF
Cosman
D
D
Galibert
L
L
D000595:Amino Acid Sequence; D000818:Animals; D023201:CD40 Ligand; D002352:Carrier Proteins; D002460:Cell Line; D002478:Cells, Cultured; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13; D002887:Chromosomes, Human, Pair 18; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D002352:Carrier Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D023201:CD40 Ligand