Heiskala M, Ståhls A, Seppälä I, Timonen T
Department of Pathology, University of Helsinki, Finland.
Nat Immun Cell Growth Regul. 1991;10(5):265-77.
Contact with natural killer (NK)-resistant monolayer targets is an inhibitory signal to NK cells. In this study, we have analyzed the effect of such effector/target cell interactions on the CD16 (FcRIII) expression on lymphocytes and the role of CD16 and interleukin-2 (IL-2) in the reactivation of their cytolytic machinery. Coculturing peripheral blood mononuclear cells with NK-resistant monolayer cells did not change the percentage of CD 16-positive effector cells, although this treatment effectively inhibited their cytotoxicity against NK-sensitive targets. The inhibited effector cells partially regained their activity by incubating for 24 h in medium supplemented with 10% fetal calf serum (FCS), whereas human albumin-, newborn calf serum- or human AB serum-supplemented media had no reactivating effect. Monoclonal class IgG1, IgG2a and IgM anti-CD16 antibodies [Abs; 3G8, CLB-CD16 (CLB-FcR gr1) and Leu 11b], and normal rabbit IgG (NR-IgG) prevented the FCS-mediated reactivation of cytotoxicity, whereas nonreactive control Abs significantly enhanced it. The detection of the CD16 antigen by the monoclonal anti-CD16 Abs Leu 11a and Leu 11c was blocked by the above anti-CD16 Abs and NR-IgG, while the expression of other NK cell-associated surface molecules (CD2, CD56) remained unchanged. Mere blocking of CD16, using a short-term incubation with anti-CD16 Abs, had an insignificant effect on endogenous NK activity, suggesting that CD16 is involved in NK cell (re)activation rather than in the killing process itself. In the presence of IL-2, inactivated effector cells also regained their killing activity. The IL-2-induced reactivation was not inhibited by anti-CD16 Abs. The results suggest that FCS-derived factors and soluble nonreactive immunoglobulins enhance the NK activity of down-regulated effector cells via CD16, and that CD16 and IL-2 receptors represent alternative independent pathways of NK cell reactivation.
与自然杀伤（NK）抗性单层靶细胞接触对NK细胞来说是一种抑制信号。在本研究中，我们分析了这种效应细胞/靶细胞相互作用对淋巴细胞上CD16（FcRIII）表达的影响，以及CD16和白细胞介素-2（IL-2）在其溶细胞机制重新激活中的作用。将外周血单核细胞与NK抗性单层细胞共培养，并未改变CD16阳性效应细胞的百分比，尽管这种处理有效地抑制了它们对NK敏感靶细胞的细胞毒性。通过在补充有10%胎牛血清（FCS）的培养基中孵育24小时，受抑制的效应细胞部分恢复了其活性，而补充有人白蛋白、新生牛血清或人AB血清的培养基则没有再激活作用。单克隆IgG1、IgG2a和IgM类抗CD16抗体[抗体；3G8、CLB-CD16（CLB-FcR gr1）和Leu 11b]以及正常兔IgG（NR-IgG）可阻止FCS介导的细胞毒性再激活，而非反应性对照抗体则显著增强了这种再激活。单克隆抗CD16抗体Leu 11a和Leu 11c对CD16抗原的检测被上述抗CD16抗体和NR-IgG阻断，而其他NK细胞相关表面分子（CD2、CD56）的表达保持不变。仅通过与抗CD16抗体短期孵育来阻断CD16，对内源性NK活性的影响不显著，这表明CD16参与NK细胞的（再）激活，而不是杀伤过程本身。在IL-2存在的情况下，失活的效应细胞也恢复了其杀伤活性。抗CD16抗体不会抑制IL-2诱导的再激活。结果表明，FCS衍生因子和可溶性非反应性免疫球蛋白通过CD16增强下调的效应细胞的NK活性, 并且CD16和IL-2受体代表NK细胞再激活的替代独立途径。
