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Division of Viral Immunology, Center for AIDS Research, Kumamoto University, and
Chemo-Sero Therapeutic Research Institute, Kyokushi, Kumamoto, Japan; and
AIDS Clinical Center, International Medical Center of Japan, Tokyo, Japan
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.
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