Bonzo/CXCR6 expression defines type 1-polarized T-cell subsets with extralymphoid tissue homing potential

J Clin Invest. 2001 Mar;107(5):595-601. doi: 10.1172/JCI11902.

Abstract

Chemokine receptor expression is finely controlled during T-cell development. We show that newly identified chemokine receptor Bonzo/CXCR6 is expressed by subsets of Th1 or T-cytotoxic 1 (Tc1) cells, but not by Th2 or Tc2 cells, establishing Bonzo as a differential marker of polarized type 1 T cells in vitro and in vivo. Priming of naive T cells by dendritic cells induces expression of Bonzo on T cells. IL-12 enhances this dendritic cell-dependent upregulation, while IL-4 inhibits it. In blood, 35-56% of Bonzo+ CD4 T cells are Th1 cells, and 60-65% of Bonzo+ CD8 T cells are Tc1 cells, while few Bonzo+ cells are type 2 T cells. Almost all Bonzo+ Tc1 cells contain preformed granzyme A and display cytotoxic effector phenotype. Most Bonzo+ T cells lack L-selectin and/or CCR7, homing receptors for lymphoid tissues. Instead, Bonzo+ T cells are dramatically enriched among T cells in tissue sites of inflammation, such as rheumatoid joints and inflamed livers. Bonzo may be important in trafficking of effector T cells that mediate type 1 inflammation, making it a potential target for therapeutic modulation of inflammatory diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Arthritis / immunology
  • Cell Differentiation
  • Cells, Cultured
  • Cytokines / pharmacology
  • Dendritic Cells / immunology
  • Gene Expression / drug effects
  • Humans
  • Immunologic Memory
  • Inflammation / immunology*
  • Liver / immunology
  • Liver Cirrhosis / immunology
  • Lymphocyte Subsets / classification
  • Lymphocyte Subsets / immunology
  • Receptors, CXCR6
  • Receptors, Chemokine
  • Receptors, Cytokine / metabolism*
  • Receptors, G-Protein-Coupled*
  • Receptors, Lymphocyte Homing / metabolism
  • Receptors, Virus*
  • Synovial Fluid / immunology
  • T-Lymphocytes, Cytotoxic / classification*
  • T-Lymphocytes, Cytotoxic / immunology
  • Th1 Cells / classification*
  • Th1 Cells / immunology

Substances

  • CXCR6 protein, human
  • Cytokines
  • Receptors, CXCR6
  • Receptors, Chemokine
  • Receptors, Cytokine
  • Receptors, G-Protein-Coupled
  • Receptors, Lymphocyte Homing
  • Receptors, Virus