Differential expression and function of L-selectin on CD56bright and CD56dim natural killer cell subsets.
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-beta 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-alpha. 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.
Frey
M
M
Department of Molecular Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Packianathan
N B
NB
Fehniger
T A
TA
Ross
M E
ME
Wang
W C
WC
Stewart
C C
CC
Caligiuri
M A
MA
Evans
S S
SS
D016475:3T3 Cells; D000818:Animals; D019002:CD56 Antigen / Q000096:biosynthesis* / Q000378:metabolism; D002478:Cells, Cultured; D003432:Cross-Linking Reagents; D016207:Cytokines / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004729:Endothelium, Lymphatic / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D019041:L-Selectin / Q000096:biosynthesis* / Q000187:drug effects / Q000502:physiology*; D008198:Lymph Nodes / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008351:Mannans / Q000378:metabolism; D008360:Mannosephosphates / Q000378:metabolism; D051379:Mice; D011485:Protein Binding / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D019002:CD56 Antigen; D003432:Cross-Linking Reagents; D016207:Cytokines; D016169:Lymphocyte Function-Associated Antigen-1; D008351:Mannans; D008360:Mannosephosphates; D019041:L-Selectin; C065532:mannose-6-phosphate rich phosphomannan; D013755:Tetradecanoylphorbol Acetate