Evidence for NK cell subsets based on chemokine receptor expression

To help understand the role of chemokines in NK cell trafficking, we determined the chemokine receptor profiles of three different human NK cell lines and freshly isolated primary human NK cells. The cell lines overlapped in their chemokine receptor profiles: CXCR3 and CXCR4 were expressed by all three lines, whereas CCR1, CCR4, CCR6, CCR7, and CX3CR1 were expressed by only one or two of the lines, and no other chemokine receptors were detected. Freshly isolated primary NK cells were found to express CXCR1, CXCR3, and CXCR4, and to contain subsets expressing CCR1, CCR4, CCR5, CCR6, CCR7, CCR9, CXCR5, and CXCR6. With the exception of CCR4, these chemokine receptors were expressed at higher percentages by CD56(bright) NK cells than by CD56(dim) NK cells. In particular, CCR7 was expressed by almost all CD56(bright) NK cells but was not detected on CD56(dim) NK cells. CCR9 and CXCR6 have not been described previously on primary NK cells. These results indicate that within both the CD56(bright) and CD56(dim) NK cell populations, subsets with the capacity for differential trafficking programs exist, which likely influence their functions in innate and adaptive immunity.