Bonzo/CXCR6 expression defines type 1–polarized T-cell subsets with extralymphoid tissue homing potential
Chang H. Kim, … , Harry B. Greenberg, Eugene C. Butcher
Chang H. Kim, … , Harry B. Greenberg, Eugene C. Butcher
Published March 1, 2001
Citation Information: J Clin Invest. 2001;107(5):595-601. https://doi.org/10.1172/JCI11902.
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Article

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.

Authors

Chang H. Kim, Eric J. Kunkel, Judie Boisvert, Brent Johnston, James J. Campbell, Mark C. Genovese, Harry B. Greenberg, Eugene C. Butcher

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Figure 4

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Bonzo is expressed on activated lymphocytes in tissue sites. FACS analys...
Bonzo is expressed on activated lymphocytes in tissue sites. FACS analysis of lymphocytes in the synovial fluid (SF) from patients with psoriatic arthritis (a) or rheumatoid arthritis (b) revealed that Bonzo is expressed on approximately 30% of both CD4 (range 24–35%) and CD8 (range 20–31%) lymphocytes in PsA and about 60–68% of CD4 and about 61–70% of CD8 T cells in RA, all of which expressed the activation marker CD69. In inflamed (alcoholic and HCV+) cirrhotic livers, Bonzo was expressed at high levels on CD69+ CD4 (range 3–11% for CD69– and 24–56% for CD69+) and CD8 (range 7–60% for CD69– and 50–91% for CD69+) lymphocytes (c). Bonzo expression was also high on TCR-αβ–CD56+ NK cells (50–92%) and TCR-αβ+CD56+ T cells (64–89%) expressing CD69 (d). Representative Bonzo expression from an alcoholic cirrhotic liver is shown (c and d). Number of independent tissue samples of each type examined (n) is shown.