CXCR6 is expressed on T cells in both T helper type 1 (Th1) inflammation and allergen-induced Th2 lung inflammation but is only a weak mediator of chemotaxis

Immunology. 2007 Aug;121(4):555-64. doi: 10.1111/j.1365-2567.2007.02603.x. Epub 2007 Apr 16.

Abstract

Numerous chemokine receptors are increased in number on T cells in inflamed tissues. Our objective was to examine CXCR6 expression on lymphocytes during immune and inflammatory reactions and its potential for mediating T-cell recruitment. The cDNA for rat CXCR6 was cloned and monoclonal antibodies (mAbs) to CXCR6 were developed. CXCR6 was present on 4-6% of CD4 and CD8 T cells in blood, normal lymph nodes (LNs) and the spleen, primarily on memory T cells. In vitro antigen re-stimulation of LN T cells from animals with autoimmune arthritis and experimental autoimmune encephalomyelitis (EAE) increased the proportion of CXCR6(+) T cells to 35-50% and anti-T-cell receptor (TCR) activation to 60-80%. In vivo, after antigen challenge of LNs there was only a small increase in CXCR6(+) T cells on the lymphoblasts in the LNs, and a much higher percentage of T cells were CXCR6(+) in virus-induced peritoneal exudates (approximately 47%) and in allergen-induced lung inflammation (33%). Chemotaxis of CXCR6-expressing inflammatory T cells to CXCL16 was poor, but that to CXCL10 was robust. We conclude that few T cells in normal and antigen-challenged LNs are CXCR6(+), whereas a high proportion of in vitro activated T cells and T cells from inflammatory sites are CXCR6(+), but these cells migrate poorly to CXCL16. This suggests that CXCR6 may contribute to T-cell positioning and activation, rather than recruitment. CXCR6 is also expressed on T cells not only in T helper type 1 (Th1) inflammation (arthritis and EAE) but also, as shown here, in Th2 inflammation, where it is increased after allergen challenge.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology
  • Animals
  • Antibodies, Monoclonal / immunology
  • Asthma / immunology
  • CHO Cells
  • Cells, Cultured
  • Chemotaxis, Leukocyte / immunology*
  • Cricetinae
  • Cricetulus
  • DNA, Complementary / genetics
  • Flow Cytometry
  • Inflammation / immunology*
  • Lymphocyte Activation / immunology
  • Lymphoid Tissue / immunology
  • Male
  • Peritonitis / immunology
  • Rats
  • Rats, Inbred BN
  • Rats, Inbred Lew
  • Receptors, CXCR6
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / immunology
  • Receptors, Chemokine / metabolism*
  • Th1 Cells / immunology*
  • Th2 Cells / immunology*
  • Up-Regulation / immunology

Substances

  • Allergens
  • Antibodies, Monoclonal
  • CXCR6 protein, rat
  • DNA, Complementary
  • Receptors, CXCR6
  • Receptors, Chemokine