title: Lymphotoxin alpha 1 beta 2: a critical mediator in V alpha 14i NKT cell differentiation.
abstract: Lymphotoxin (LT) alpha 1 beta 2, a tumour necrosis factor (TNF) cytokine critically involved in lymphoid organogenesis, is indispensable for the differentiation of V alpha 14i natural killer T (NKT) cells, a lymphocyte subset with important immunoregulatory properties. However, it is not required for the development of conventional T-cells. LT alpha 1 beta 2 signals through the LT beta receptor, which is expressed on non-lymphoid cells. Triggering of this receptor induces a unique signalling cascade leading to the activation of the transcription factor RelB through activation of NF-kappa B inducing kinase. This pathway is required for V alpha 14i NKT cell differentiation as appears from studies in gene-deficient animals. By reciprocal bone marrow chimeras, it was shown that RelB is required in a radiation-resistant host cell or stromal cell for normal V alpha 14i NKT cell development, presumably in the thymic stroma. These stromal cells are not required for the positive selection of these cells but rather play a prominent role in their terminal differentiation. Altogether, these observations underscore the unique developmental requirements of this particular lymphocyte subset.
authors.affiliation: Laboratory of Pharmaceutical Biotechnology, Gent University, Belgium.
authors.forename: Ann Sophie
authors.initials: AS
authors.lastname: Franki
authors.forename: Katrien
authors.initials: K
authors.lastname: Van Beneden
authors.forename: Pieter
authors.initials: P
authors.lastname: Dewint
authors.forename: Ivan
authors.initials: I
authors.lastname: Meeus
authors.forename: Eric
authors.initials: E
authors.lastname: Veys
authors.forename: Dieter
authors.initials: D
authors.lastname: Deforce
authors.forename: Dirk
authors.initials: D
authors.lastname: Elewaut
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007694:Killer Cells, Natural / Q000276:immunology*; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha / Q000276:immunology / Q000502:physiology*; D053308:Lymphotoxin-beta; D008565:Membrane Proteins / Q000276:immunology / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000276:immunology / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000502:physiology; D017154:Stromal Cells / Q000276:immunology / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000276:immunology / Q000378:metabolism
chemical_list: D007135:Immunoglobulin Variable Region; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D018124:Receptors, Tumor Necrosis Factor; D014157:Transcription Factors; D051841:Transcription Factor RelB