Tarkkanen J, Saksela E, Lanier L L
J Immunol. 1986 Oct 15;137(8):2428-33.
We showed previously that contact of human peripheral blood lymphocytes with glutaraldehyde-fixed Salmonella bacteria augmented their cytotoxic capacity against NK-sensitive targets. We have now analyzed the characteristics of the activation and also identified the subsets of lymphocytes responding to bacterial contact. Blocking of protein synthesis with cyclohexamide totally abrogated bacterial induction of activated killing (AK), whereas inhibition of DNA synthesis with mitomycin C did not significantly affect the capacity of lymphocytes to respond to bacterial contact. Both the induction and the effector phase of AK were radioresistant. The AK cells exhibited efficient lytic activity, comparable to that induced by recombinant IL 2 (rIL 2), against NK-resistant targets (including both hematopoietic and solid tumor cell lines). All inducible cytotoxic activity was contained within the subset of lymphocytes expressing Leu-19 (NKH-1) antigen. Leu-19- lymphocytes exhibited no significant NK activity and could not be further stimulated by bacterial contact, rIL 2, or IFN-alpha. Within the Leu-19+ lymphocyte subset, two distinct cell types were present; CD3-, Leu-19+ NK cells and CD3+. Leu-19+ T cells. The CD3+, Leu-19+, T cells mediated low levels of non-MHC-restricted cytotoxicity against K562, but did not respond to bacterial contact, even though rIL 2 could augment their lytic activity slightly. However, the cytotoxic activity of CD3-, Leu-19+ NK cells was significantly augmented by bacterial contact. Within the CD3-, Leu-19+ NK cell population both CD16+ and CD16- cells responded to bacterial activation. The CD3-, CD16-, Leu-19+ cells constituted 1 to 4% of the Percoll-fractionated low buoyant density lymphocytes and accounted for the activation seen within the CD16- lymphocyte population. Thus bacterial stimulation of NK activity seems to be mediated for the most part via CD16+, Leu-19+ cells, and a minor overall contribution is mediated via CD3-, CD16-, Leu-19+ cells. No apparent involvement of T cells was seen in the lytic response of lymphocytes to bacterial contact.
我们之前的研究表明，人外周血淋巴细胞与戊二醛固定的沙门氏菌接触可增强其对NK敏感靶标的细胞毒性能力。我们现在分析了这种激活的特征，并确定了对细菌接触有反应的淋巴细胞亚群。用环己酰胺阻断蛋白质合成完全消除了细菌诱导的活化杀伤（AK），而用丝裂霉素C抑制DNA合成并未显著影响淋巴细胞对细菌接触的反应能力。AK的诱导阶段和效应阶段均具有抗辐射性。AK细胞对NK抗性靶标（包括造血和实体瘤细胞系）表现出高效的裂解活性，与重组IL-2（rIL-2）诱导的活性相当。所有可诱导的细胞毒性活性都包含在表达Leu-19（NKH-1）抗原的淋巴细胞亚群中。Leu-19-淋巴细胞没有明显的NK活性，并且不能被细菌接触、rIL-2或IFN-α进一步刺激。在Leu-19+淋巴细胞亚群中，存在两种不同的细胞类型；CD3-、Leu-19+NK细胞和CD3+、Leu-19+T细胞。CD3+、Leu-19+T细胞对K562介导低水平的非MHC限制性细胞毒性，但对细菌接触无反应，尽管rIL-2可轻微增强其裂解活性。然而，细菌接触显著增强了CD3-、Leu-19+NK细胞的细胞毒性活性。在CD3-、Leu-19+NK细胞群体中，CD16+和CD16-细胞均对细菌激活有反应。CD3-、CD16-、Leu-19+细胞占Percoll分级的低浮力密度淋巴细胞的1%至4%，并解释了CD16-淋巴细胞群体中观察到的激活现象。因此，细菌对NK活性的刺激似乎在很大程度上是通过CD16+、Leu-19+细胞介导的，而CD3-、CD16-、Leu-19+细胞介导的总体贡献较小。在淋巴细胞对细菌接触的裂解反应中未观察到T细胞有明显参与。
