Bonzo/CXCR6 expression defines type 1-polarized T-cell subsets with extralymphoid tissue homing potential.
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.
Laboratory of Immunology and Vascular Biology, Department of Pathology, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA. chkim@stanford.edu
C H
CH
Kim
E J
EJ
Kunkel
J
J
Boisvert
B
B
Johnston
J J
JJ
Campbell
M C
MC
Genovese
H B
HB
Greenberg
E C
EC
Butcher
D001168:Arthritis / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology*; D008099:Liver / Q000276:immunology; D008103:Liver Cirrhosis / Q000276:immunology; D016131:Lymphocyte Subsets / Q000145:classification / Q000276:immunology; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D011991:Receptors, Virus; D013582:Synovial Fluid / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification* / Q000276:immunology; D018417:Th1 Cells / Q000145:classification* / Q000276:immunology
C106330:CXCR6 protein, human; D016207:Cytokines; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D043562:Receptors, G-Protein-Coupled; D016201:Receptors, Lymphocyte Homing; D011991:Receptors, Virus