Distinct phenotypic and functional characteristics of human natural killer cells obtained by rapid interleukin 2-induced adherence to plastic.
Human natural killer (NK) cells can be functionally subdivided into adherent (A) and non-adherent (NA) subpopulations. In the presence of 22 nM 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 nM. This adherence was blocked completely by antibody to IL2 receptor (IL2R)-beta and, partially, by antibodies to beta 1 or beta 2 integrins, ICAM-1, CD2 or LFA3, but not by antibodies to the IL2R-alpha or CD56 antigen. A-NK cells separated from NA-NK cells after 5 hr of incubation in the presence of IL2 were significantly (P < 0.05) enriched in CD56dimCD16dim or -IL2Rp55+ and IL2Rp75+ cells, but were depleted of CD56bright CD16- cells. While surface density of CD56 and CD16 antigens was lower, that of beta 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 nM 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 nM 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 nM 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-CD56dim or -CD16dim or -beta 2integrinsbrightIL2Rp75+), rapid expression of IL2R-alpha, higher NK activity, delayed development of LAK activity, and ability to respond optimally in the presence of 22 nM of IL2.(ABSTRACT TRUNCATED AT 400 WORDS)
Vujanovic
N L
NL
Department of Pathology, University of Pittsburgh School of Medicine, Pennsylvania.
Rabinowich
H
H
Lee
Y J
YJ
Jost
L
L
Herberman
R B
RB
Whiteside
T L
TL
D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000097:blood; D002455:Cell Division / Q000502:physiology; D002469:Cell Separation / Q000379:methods*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000502:physiology*; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology; D007694:Killer Cells, Natural / Q000502:physiology*; D010969:Plastics; D015375:Receptors, Interleukin-2 / Q000502:physiology
D015815:Cell Adhesion Molecules; D007376:Interleukin-2; D010969:Plastics; D015375:Receptors, Interleukin-2