LAT regulates gammadelta T cell homeostasis and differentiation

Nat Immunol. 2003 Oct;4(10):999-1008. doi: 10.1038/ni977. Epub 2003 Sep 14.

Abstract

LAT (linker for activation of T cells) is essential for T cell receptor signaling. Mice homozygous for a mutation of the three C-terminal LAT tyrosine residues showed a block in alphabeta T cell development and a partially impaired gammadelta T cell development. Without intentional immunization, they accumulated gammadelta T cells in the spleen and lymph nodes that chronically produced T helper type 2 cytokines in large amounts, and caused the maturation of plasma cells secreting immunoglobulin E (IgE) and IgG1. These effects are very similar to that triggered in the alphabeta lineage by a mutation involving a distinct LAT tyrosine. Thus, LAT is an essential regulator of T cell homeostasis and terminal differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Base Sequence
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology*
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cytokines / immunology
  • Flow Cytometry
  • Homeostasis / immunology
  • Immunohistochemistry
  • Lymphocyte Activation / immunology
  • Membrane Proteins*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Molecular Sequence Data
  • Mutation
  • Phenotype
  • Phosphoproteins / genetics
  • Phosphoproteins / immunology*
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Spleen / immunology
  • T-Lymphocytes / immunology*
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Tyrosine / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Cytokines
  • Lat protein, mouse
  • Membrane Proteins
  • Phosphoproteins
  • Receptors, Antigen, T-Cell, gamma-delta
  • Tyrosine