Increased chemokine receptor CCR7/EBI1 expression enhances the infiltration of lymphoid organs by adult T-cell leukemia cells.
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)
Hasegawa
H
H
First Department of Internal Medicine, Ehime University School of Medicine, Shigenobu, Ehime 791-0295, Japan. hitoshih@m.ehime-u.ac.jp
Nomura
T
T
Kohno
M
M
Tateishi
N
N
Suzuki
Y
Y
Maeda
N
N
Fujisawa
R
R
Yoshie
O
O
Fujita
S
S
D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002448:Cell Adhesion; D002460:Cell Line; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000502:physiology; D002634:Chemotaxis, Leukocyte; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000097:blood / Q000235:genetics / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000032:analysis; D008198:Lymph Nodes / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010581:Peyer's Patches / Q000276:immunology; D054400:Receptors, CCR7; D011956:Receptors, Cell Surface / Q000235:genetics*; D019707:Receptors, Chemokine / Q000235:genetics*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*
C515478:CCL21 protein, human; C515370:CCR7 protein, human; D054421:Chemokine CCL21; D019742:Chemokines, CC; D054400:Receptors, CCR7; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D018799:Intercellular Adhesion Molecule-1; D017493:Leukocyte Common Antigens