Lymphotoxin alpha 1 beta 2: a critical mediator in V alpha 14i NKT cell differentiation.
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.
Franki
Ann Sophie
AS
Laboratory of Pharmaceutical Biotechnology, Gent University, Belgium.
Van Beneden
Katrien
K
Dewint
Pieter
P
Meeus
Ivan
I
Veys
Eric
E
Deforce
Dieter
D
Elewaut
Dirk
D
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
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