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,§

,§
Departments of
*
Molecular Immunology,
Medicine, and
Flow Cytometry, Roswell Park Cancer Institute, Buffalo, NY 14263; and
§
Department of Hematology/Oncology, Arthur G. James Cancer Hospital and Research Institute, Ohio State University, Columbus, OH 43210
NK cells are the first line of defense against foreign cells,
virally infected cells, and tumors. The mechanisms whereby NK cells
accumulate in extralymphoid sites in response to pathogenic stimuli are
not well understood. The L-selectin adhesion molecule (CD62L) plays a
primary role in mediating the initial interaction of leukocytes with
vascular endothelium, a crucial step in the extravasation of immune
effector cells into tissues. In this report, we show L-selectin to be
uniquely expressed on a subset of resting human NK cells
(CD56bright). Notably, CD56bright NK
cells expressed L-selectin at a higher density than all other
peripheral blood leukocytes. NK activation by PMA, IL-2, IL-15, or
TGF-ß down-regulated L-selectin on the CD56bright subset,
while increased L-selectin levels were observed in both the
CD56bright and CD56dim NK subsets in response
to IL-12, IL-10, or IFN-
. Moreover, CD56bright NK cells
bound with high efficiency to physiologic L-selectin ligands on
peripheral lymph node high endothelial venules (HEV). In sharp
contrast, CD56dim NK cells adhered poorly to HEV and were
predominantly L-selectin- or expressed L-selectin only at
low density. In CD56bright cells and a subpopulation of
CD56dim cells, L-selectin ligation by mAb cross-linking
activated lymphocyte function-associated Ag 1 (LFA-1), a second
adhesion molecule required for leukocyte extravasation. LFA-1 was
expressed on both NK subsets, although its density was constitutively
higher on CD56dim cells. Taken together, evidence of
differential expression of L-selectin and LFA-1 on
CD56bright and CD56dim NK subsets strongly
suggests unique migratory properties and functions of these cells
during the early immune response to foreign pathogens.
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