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 tis sues by circulating ATL cells, a finding often associated with a poor progn osis. Leukocyte migration from the circulation into tissues depends on inte grin-mediated adhesion to the endothelium, and integrins are tightly regula ted by several factors, such as chemokines. In this study, we focused on th e interaction between chemokines and chemokine receptors on ATL cells to un derstand factors involved in ATL cell infiltration of lymphoid organs. We c ompared freshly isolated ATL cells from patients with and without lymphoid organ involvement for the expression of the chemokine receptor CCR7/EBI1, t he 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), reveal ed that ATL cells from patients with lymphoid organ involvement expressed s ignificantly more CCR7/EBI1 than control CD4(+)CD45RO(+) T cells and AIL ce lls from patients without lymphoid organ involvement. Consequently, signifi cantly more ATL cells from patients with lymphoid organ Involvement than co ntrol CD4(+)CD45RO(+) T cells and ATL cells from patients without lymphoid organ involvement adhered to surfaces costed with ICAM-1 and SLC or EBI1-li gand chemokine (ELC), another ligand for CCR7/EBI1, under static and flow c onditions 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. (C) 2000 by The American Society of Hematology.