Functional expression of the chemokine receptor CCR5 on virus epitope-specific memory and effector CD8+ T cells

Because the chemokine receptor CCR5 is expressed on Th1 CD4(+) cells, it is important to investigate the expression and function of this receptor on other T cells involved in Th1 immune responses, such as Ag-specific CD8(+) T cells, which to date have been only partially characterized. Therefore, we analyzed the expression and function of CCR5 on virus-specific CD8(+) T cells identified by HLA class I tetramers. Multicolor flow cytometry analysis demonstrated that CCR5 is expressed on memory (CD28(+)CD45RA(-)) and effector (CD28(-)CD45RA(-) and CD28(-)CD45RA(+)) CD8(+) T cells but not on naive (CD28(+)CD45RA(+)) CD8+ T cells. CCR5 expression was much lower on two effector CD8(+) T cells than on memory CD8(+) T cells. Analysis of CCR7 and CCR5 expression on the different types of CD8(+) T cells showed that memory CD8(+) T cells have three phenotypic subsets, CCR5(+)CCR7(-), CCR5(+)CCR7(+), and CCR5(-)CCR7(+), while naive and effector CD8(+) T cells have CCR5-CCR7+ and CCR5(+)CCR7(-) phenotypes, respectively. These results suggest the following sequence for differentiation of memory CD8(+) T cells: CCR5(-)CCR7(+)--> CCR5(+)CCR7(+-->)CCR5(+)CCR7(-). CCR5(+)CD8(+) T cells effectively migrated in response to RANTES, suggesting that CCR5 plays a critical role in the migration of Ag-specific effector and differentiated memory CD8(+) T cells to inflammatory tissues and secondary lymphoid tissues. This is in contrast to CCR7, which functions as a homing receptor in migration of naive and memory CD8(+) T cells to secondary lymphoid tissues.