Lymphotoxin alpha 1 beta 2: a critical mediator in V alpha 14i NKT cell differentiation

Mol Immunol. 2005 Feb;42(4):413-7. doi: 10.1016/j.molimm.2004.07.020.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor*
  • Immunoglobulin Variable Region / genetics*
  • Killer Cells, Natural / immunology*
  • Lymphotoxin beta Receptor
  • Lymphotoxin-alpha / immunology
  • Lymphotoxin-alpha / physiology*
  • Lymphotoxin-beta
  • Membrane Proteins / immunology
  • Membrane Proteins / physiology*
  • Proto-Oncogene Proteins / immunology
  • Proto-Oncogene Proteins / metabolism
  • Receptors, Tumor Necrosis Factor / immunology
  • Receptors, Tumor Necrosis Factor / physiology
  • Stromal Cells / immunology
  • Stromal Cells / physiology
  • T-Lymphocyte Subsets / immunology*
  • Transcription Factor RelB
  • Transcription Factors / immunology
  • Transcription Factors / metabolism


  • Immunoglobulin Variable Region
  • Lymphotoxin beta Receptor
  • Lymphotoxin-alpha
  • Lymphotoxin-beta
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Receptors, Tumor Necrosis Factor
  • Transcription Factors
  • Transcription Factor RelB