Human natural killer cell adhesion molecules. Differential expression after activation and participation in cytolysis.
Cell adhesion molecules (CAM) participate in interactions between lymphocytes, accessory cells, and target cells that are critical in the generation of effective immune responses. To characterize the involvement of CAM in NK and lymphokine activated killer (LAK) activities, we examined the expression of several CAM by freshly isolated human NK cells and by NK cells activated in vitro with IL-2, and compared this to CAM expression by T lymphocytes under similar conditions. Freshly isolated human NK cells were uniformly LFA-3 (CD58)+ and expressed two to three-fold higher surface levels of LFA-1 (CD11a/CD18) than resting T lymphocytes. More NK cells than T cells also expressed phenotypically detectable levels of intercellular adhesion molecule-1 (CD54). After in vitro incubation with IL-2, human NK cells demonstrated four- to sixfold increases in surface levels of CD11a/CD18, CD2, CD54, CD58, and the NK cell-associated Ag NKH-1 (CD56). Furthermore, essentially all NK cells became CD54+ within 3 days of exposure to IL-2. T cells did not demonstrate comparable up-regulation of CAM after incubation with IL-2. Increases in NK cell CAM expression were associated with enhanced formation of E:T cell conjugates, enhanced killing of NK-sensitive targets, and the induction of cytotoxicity for previously NK-resistant targets (LAK activity). The LAK activity induced by exogenous IL-2 could be partially inhibited by anti-CD2, anti-CD11a, or anti-CD54 antibodies and almost completely abrogated by anti-CD2 and anti-CD11a in combination. These studies suggest that CAM play a central role in the regulation of NK cytolysis, and that changes in CAM expression may alter the target cell specificity of activated NK effectors.
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
M J
MJ
Robertson
M A
MA
Caligiuri
T J
TJ
Manley
H
H
Levine
J
J
Ritz
D000911:Antibodies, Monoclonal / Q000276:immunology; D000943:Antigens, Differentiation / Q000032:analysis*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D018845:CD11 Antigens; D018821:CD18 Antigens; D018801:CD2 Antigens; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules / Q000032:analysis* / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D011971:Receptors, Immunologic / Q000032:analysis*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D016028:Receptors, Leukocyte-Adhesion / Q000032:analysis*; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018845:CD11 Antigens; D018821:CD18 Antigens; D018801:CD2 Antigens; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D016028:Receptors, Leukocyte-Adhesion; D018799:Intercellular Adhesion Molecule-1