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Blood, 1 March 2002, Vol. 99, No. 5, pp. 1505-1511
CHEMOKINES
Frequent expression of CCR4 in adult T-cell leukemia and human
T-cell leukemia virus type 1-transformed T cells
Osamu Yoshie,
Ryuichi Fujisawa,
Takashi Nakayama,
Hitomi Harasawa,
Hideaki Tago,
Dai Izawa,
Kunio Hieshima,
Youichi Tatsumi,
Kouji Matsushima,
Hitoshi Hasegawa,
Akihisa Kanamaru,
Shimeru Kamihira, and
Yasuaki Yamada
From the Departments of Microbiology and Internal
Medicine III, Kinki University School of Medicine, Department of
Neurology, Tohoku University School of Medicine, Department of
Laboratory Medicine, Nagasaki University School of Medicine, Department
of Molecular Preventive Medicine, Tokyo University School of Medicine,
Department of Internal Medicine, Ehime University School of Medicine,
Japan.
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.
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