Frequent expression of CCR4 in adult T-cell leukemia and human T-cell leukemia virus type 1-transformed T cells.
Chemokines and chemokine receptors play important roles in migration and tissue localization of various lymphocyte subsets. Here, we report the highly frequent expression of CCR4 in adult T-cell leukemia (ATL) and human T-cell leukemia virus type 1 (HTLV-1)-immortalized T cells. Flow cytometric analysis revealed that ATL and HTLV-1-immortalized T-cell lines consistently expressed CCR4. Inducible expression of HTLV-1 transcriptional activator tax in a human T-cell line Jurkat did not, however, up-regulate CCR4 mRNA. In vitro immortalization of peripheral blood T cells led to preferential outgrowth of CD4(+) T cells expressing CCR4. We further demonstrated highly frequent expression of CCR4 in fresh ATL cells by (1) reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of CCR4 expression in peripheral blood mononuclear cells (PBMCs) from patients with ATL and healthy controls; (2) flow cytometric analysis of CCR4-expressing cells in PBMCs from patients with ATL and healthy controls; (3) CCR4 staining of routine blood smears from patients with ATL; and (4) an efficient migration of fresh ATL cells to the CCR4 ligands, TARC/CCL17 and MDC/CCL22, in chemotaxis assays. Furthermore, we detected strong signals for CCR4, TARC, and MDC in ATL skin lesions by RT-PCR. Collectively, most ATL cases have apparently derived from CD4(+) T cells expressing CCR4. It is now known that circulating CCR4(+) T cells are mostly polarized to Th2 and also contain essentially all skin-seeking memory T cells. Thus, HTLV-1-infected CCR4(+) T cells may have growth advantages by deviating host immune responses to Th2. CCR4 expression may also account for frequent infiltration of ATL into tissues such as skin and lymph nodes.
Yoshie
Osamu
O
Department of Microbiology, Kinki University School of Medicine, Osaka, Japan. o.yoshie@med.kindai.ac.jp
Fujisawa
Ryuichi
R
Nakayama
Takashi
T
Harasawa
Hitomi
H
Tago
Hideaki
H
Izawa
Dai
D
Hieshima
Kunio
K
Tatsumi
Youichi
Y
Matsushima
Kouji
K
Hasegawa
Hitoshi
H
Kanamaru
Akihisa
A
Kamihira
Shimeru
S
Yamada
Yasuaki
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002461:Cell Line, Transformed; D019742:Chemokines, CC / Q000378:metabolism / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D005260:Female; D016356:Gene Products, tax / Q000494:pharmacology; D015368:Human T-lymphotropic virus 1; D006801:Humans; D019169:Jurkat Cells; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000187:drug effects; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D012867:Skin / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology / Q000821:virology
C515354:CCR4 protein, human; D019742:Chemokines, CC; D016356:Gene Products, tax; D012333:RNA, Messenger; D054398:Receptors, CCR4; D019707:Receptors, Chemokine