T cell, Ig domain, mucin domain-2 gene-deficient mice reveal a novel mechanism for the regulation of Th2 immune responses and airway inflammation

J Immunol. 2006 Oct 1;177(7):4311-21. doi: 10.4049/jimmunol.177.7.4311.

Abstract

The development of asthma and other atopic diseases is influenced by cytokines produced by Th2 effector T cells. How effector T cell responses are regulated once these cell populations are established remains unclear. The recently described T cell and airway phenotype regulator locus, containing the T cell, Ig domain, mucin domain (TIM) genes, is genetically associated with Th2 cytokine production and Th2-dependent immune responses. In this study, we report the phenotype of the TIM-2 gene-deficient mouse, and demonstrate exacerbated lung inflammation in an airway atopic response model. Immune responses in the TIM-2-deficient mouse reveal disregulated expression of Th2 cytokines, and adoptive transfer experiments show that the T cell compartment is responsible for the heightened inflammatory phenotype. These studies show that TIM-2 is a novel and critical regulator of effector T cell activity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Asthma / immunology
  • Cell Differentiation
  • Disease Models, Animal
  • Flow Cytometry
  • Inflammation / immunology*
  • Lung / immunology*
  • Lung / metabolism
  • Lung / pathology
  • Membrane Proteins / deficiency*
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Mutant Strains
  • Ovalbumin / immunology
  • Rats
  • Recombinant Fusion Proteins / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • Th2 Cells / cytology
  • Th2 Cells / immunology*

Substances

  • Membrane Proteins
  • Recombinant Fusion Proteins
  • Ovalbumin