Distinct Phenotypic and Functional Characteristics of Human Natural Killer Cells Obtained by Rapid Interleukin 2-Induced Adherence to Plastic

• Published in: Cellular immunology Vol. 151; no. 1; pp. 133 - 157
• Main Authors: Vujanovic, Nikola L., Rabinowich, Hannah, Lee, Young Jo, Jost, Lorenz, Herberman, Ronald B., Whiteside, Theresa L.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.10.1993
• Subjects: Cell Adhesion; Cell Adhesion Molecules - blood; Cell Division - physiology; Cell Separation - methods; Cells, Cultured; Cytotoxicity, Immunologic - physiology; Humans; Immunophenotyping; Interleukin-2 - physiology; Killer Cells, Lymphokine-Activated - physiology; Killer Cells, Natural - physiology; Plastics; Receptors, Interleukin-2 - physiology
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1006/cimm.1993.1227

Human natural killer (NK) cells can be functionally subdivided into adherent (A) and nonadherent (NA) subpopulations. In the presence of 22 n M of interleukin 2(IL2), a substantial proportion of resting (R)-NK cells developed adherence to plastic as early as after 5 min of IL2 incubation, and by 1-5 hr of IL2 induction, 16% (range, 4-30%) of NK cells were adherent. Optimal concentration of IL2 for adherence of NK cells was 2-22 n M. This adherence was blocked completely by antibody to IL2 receptor (IL2R)-β and, partially, by antibodies to β 1 or β 2 integrins, ICAM-1, CD2 or LFA3, but not by antibodies to the IL2R-α or CD56 antigen. ANK cells separated from NA-NK cells after 5 hr of incubation in the presence of IL2 were significantly ( P<0.05) enriched in CD56 dimCD16 dim or -IL2Rp55 + and IL2Rp75 + cells, but were depleted of CD56 bright CD16 - cells. While surface density of CD56 and CD16 antigens was lower, that of β 2 integrins (CD18, CD11a, CD11b) was higher on A-NK than on NA-NK cells. In a single-cell cytotoxicity assay, 61% of A-NK vs 37% of NA-NK cells bound, and 24% of A-NK vs 11% of NA-NK cells killed, K562 targets. In 4-day cultures with 0.02 or 2.2 n M of IL2, A-NK cells developed lymphokine-activated killer (LAK) activity later than NA-NK cells. By autoradiography, three to eight times more A-NK than NA-NK cells incorporated [ 3H]TdR into cell nuclei between 48 and 96 hr of IL2 incubation. In 14-day cultures in the presence of 22 n M of IL2, A-NK cells, which were initially adherent but later grew as single-cell suspensions, proliferated better (30-fold; P<0.03) and expressed lower membrane density of CD56 than NA-NK cells. In culture, A-NK cells had consistently higher cytotoxicity against K562 targets than NA-NK cells, but cytotoxicity against Daudi was similar for both subsets. The data indicate that short incubation (1-5 hr) of human NK cells in the presence of 22 n M of IL2 allows for selection of a subpopulation which differs from the rest of NK cells not only by properties of rapid adherence to plastic, but also by a characteristic phenotype (CD3 -CD56 dim or- CD16 dim or -β 2integrins brightIL2Rp75 +), rapid expression of IL2R-α, higher NK activity, delayed development of LAK activity, and ability to respond optimally in the presence of 22 n M of IL2. Thus, A-NK cells appear to be a phenotypically and functionally distinct subset of mature NK cells.