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Blood, Vol. 95 No. 1 (January 1), 2000:
pp. 30-38
Increased chemokine receptor CCR7/EBI1 expression enhances the
infiltration of lymphoid organs by adult T-cell leukemia cells
Hitoshi Hasegawa,
Tetsuhiko Nomura,
Masashi Kohno,
Norihiko Tateishi,
Yoji Suzuki,
Nobuji Maeda,
Ryuichi Fujisawa,
Osamu Yoshie, and
Shigeru Fujita
From the First Department of Internal Medicine, Ehime University
School of Medicine, Shigenobu, Ehime 791-0295, Japan; the Department of
Physiology, Ehime University School of Medicine, Shigenobu, Ehime
791-0295, Japan; and the Department of Bacteriology, Kinki University
School of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
Adult T-cell leukemia (ATL) is characterized by infiltration of
various tissues by circulating ATL cells, a finding often associated
with a poor prognosis. Leukocyte migration from the circulation into
tissues depends on integrin-mediated adhesion to the endothelium, and
integrins are tightly regulated by several factors, such as chemokines.
In this study, we focused on the interaction between chemokines and
chemokine receptors on ATL cells to understand factors involved in ATL
cell infiltration of lymphoid organs. We compared freshly isolated ATL
cells from patients with and without lymphoid organ involvement for the
expression of the chemokine receptor CCR7/EBI1, the functional
receptor for secondary lymphoid-tissue chemokine
(SLC), which is expressed at high levels by high endothelial venules of
lymph nodes and Peyer's patches. Reverse transcriptase-polymerase
chain reaction and flow cytometric analysis, using anti-CCR7 monoclonal
antibody (CCR7.6B3), revealed that ATL cells from patients with
lymphoid organ involvement expressed significantly more CCR7/EBI1 than control CD4+CD45RO+ T cells and ATL cells
from patients without lymphoid organ involvement. Consequently,
significantly more ATL cells from patients with lymphoid organ
involvement than control
CD4+CD45RO+ T cells and ATL cells from
patients without lymphoid organ involvement adhered to
surfaces coated with ICAM-1 and SLC or EBI1-ligand chemokine (ELC), another ligand for CCR7/EBI1, under static and flow
conditions and migrated toward SLC or ELC at a low concentration (30 ng/ml). These findings suggest that increased CCR7/EBI1 expression plays a role in lymphoid organ infiltration of ATL cells. (Blood. 2000;
30-38)
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