Rac2-deficient mice display perturbed T-cell distribution and chemotaxis, but only minor abnormalities in T(H)1 responses

Immunol Cell Biol. 2002 Jun;80(3):231-40. doi: 10.1046/j.1440-1711.2002.01077.x.

Abstract

The haematopoietic-specific RhoGTPase, Rac2, has been indirectly implicated in T-lymphocyte development and function, and as a pivotal regulator of T Helper 1 (T(H)1) responses. In other haematopoietic cells it regulates cytoskeletal rearrangement downstream of extracellular signals. Here we demonstrate that Rac2 deficiency results in an abnormal distribution of T lymphocytes in vivo and defects in T-lymphocyte migration and filamentous actin generation in response to chemoattractants in vitro. To investigate the requirement for Rac2 in IFN-gamma production and TH1 responses in vivo, Rac2-deficient mice were challenged with Leishmania major and immunized with ovalbumin-expressing cytomegalovirus. Despite a minor skewing towards a T(H)2 phenotype, Rac2-deficient mice displayed no increased susceptibility to L. major infection. Cytotoxic T-lymphocyte responses to cytomegalovirus and ovalbumin were also normal. Although Rac2 is required for normal T-lymphocyte migration, its role in the generation of T(H)1 responses to infection in vivo is largely redundant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Cell Adhesion Molecules / immunology
  • Cell Adhesion Molecules / metabolism
  • Chemokine CCL19
  • Chemokines, CC
  • Chemotaxis, Leukocyte*
  • Cytomegalovirus / immunology
  • Fibronectins / metabolism
  • Immunoglobulin G / classification
  • Immunoglobulin G / immunology
  • Immunophilins / metabolism
  • Integrin beta1 / metabolism
  • Leishmania major / cytology
  • Leishmania major / immunology
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Peptidylprolyl Isomerase*
  • T-Lymphocyte Subsets / immunology*
  • Th1 Cells / chemistry
  • Th1 Cells / immunology*
  • rac GTP-Binding Proteins / deficiency
  • rac GTP-Binding Proteins / physiology*

Substances

  • Actins
  • Ccl19 protein, mouse
  • Cell Adhesion Molecules
  • Chemokine CCL19
  • Chemokines, CC
  • Fibronectins
  • Immunoglobulin G
  • Integrin beta1
  • Membrane Proteins
  • rac2 GTP-binding protein
  • rac GTP-Binding Proteins
  • Immunophilins
  • Peptidylprolyl Isomerase