Lymphotoxin-mediated regulation of gammadelta cell differentiation by alphabeta T cell progenitors

Science. 2005 Feb 11;307(5711):925-8. doi: 10.1126/science.1103978. Epub 2004 Dec 9.

Abstract

The thymus gives rise to two T cell lineages, alphabeta and gammadelta, that are thought to develop independently of one another. Hence, double positive (DP) thymocytes expressing CD4 and CD8 coreceptors are usually viewed simply as progenitors of CD4+ and CD8+ alphabeta T cells. Instead we report that DP cells regulate the differentiation of early thymocyte progenitors and gammadelta cells, by a mechanism dependent on the transcription factor RORgt, and the lymphotoxin (LT) beta receptor (LTbetaR). This finding provokes a revised view of the thymus, in which lymphoid tissue induction-type processes coordinate the developmental and functional integration of the two T cell lineages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Lineage
  • Gene Expression
  • Genes, T-Cell Receptor
  • Ligands
  • Lymphocyte Activation
  • Lymphotoxin beta Receptor
  • Lymphotoxin-alpha / biosynthesis
  • Lymphotoxin-alpha / genetics
  • Lymphotoxin-alpha / physiology*
  • Membrane Proteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Phenotype
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
  • Receptors, Antigen, T-Cell, gamma-delta / biosynthesis
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / physiology*
  • Receptors, Thyroid Hormone / genetics
  • Receptors, Thyroid Hormone / physiology*
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / physiology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology*
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics
  • Tumor Necrosis Factor Ligand Superfamily Member 14
  • Tumor Necrosis Factor-alpha / genetics
  • Up-Regulation

Substances

  • Ligands
  • Ltbr protein, mouse
  • Lymphotoxin beta Receptor
  • Lymphotoxin-alpha
  • Membrane Proteins
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Retinoic Acid
  • Receptors, Thyroid Hormone
  • Receptors, Tumor Necrosis Factor
  • Rorc protein, mouse
  • Tnfsf14 protein, mouse
  • Transcription Factors
  • Tumor Necrosis Factor Ligand Superfamily Member 14
  • Tumor Necrosis Factor-alpha