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.
Fukada
Katsuhiko
K
Division of Viral Immunology, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kyokushi, Kumamoto 860-0811, Japan.
Sobao
Yuji
Y
Tomiyama
Hiroko
H
Oka
Shinichi
S
Takiguchi
Masafumi
M
D018106:CD28 Antigens / Q000032:analysis; D002454:Cell Differentiation; D019070:Cell Lineage; D002634:Chemotaxis, Leukocyte; D002999:Clone Cells; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000032:analysis; D019713:Receptors, CCR5 / Q000378:metabolism* / Q000502:physiology*; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
C515370:CCR7 protein, human; D018106:CD28 Antigens; D018984:Epitopes, T-Lymphocyte; D015488:HIV Antigens; D019713:Receptors, CCR5; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D017493:Leukocyte Common Antigens