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

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.