Bellone G, Trinchieri G
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
J Immunol. 1994 Aug 1;153(3):930-7.
NK cell stimulatory factor, or IL-12 (NKSF/IL-12), is a heterodimeric cytokine produced by monocyte-macrophages, B cells, and possibly other accessory cell types. Although the major biologic effects of NKSF/IL-12 have been demonstrated on mature T and NK cells, in which it induces cytokine secretion, increased cytotoxicity, and proliferation, recent evidence in the murine system has suggested that NKSF/IL-12 may play a role in the differentiation of early lymphohematopoietic progenitor cells and thymocytes. In this paper, we have analyzed the effect of human rNKSF/IL-12 on the formation of colonies by highly enriched hematopoietic progenitor cells from human peripheral blood and bone marrow. At concentrations between 1 and 10 ng/ml, NKSF/IL-12 synergizes with a combination of steel factor and IL-3 to induce formation of mixed, erythroid, and myeloid colonies. Therefore, human NKSF/IL-12, like murine NKSF/IL-12, seems to belong to a small group of early acting cytokines, including IL-6, granulocyte-CSF, leukemia-inhibitory factor, and IL-11, which are able to synergize with steel factor and IL-3 to induce proliferation and differentiation of very early hematopoietic progenitor cells. However, in the presence of enriched preparations of NK cells cultured together with the progenitor cells, NKSF/IL-12 inhibits formation of hematopoietic colonies supported by IL-3 and granulocyte-macrophage CSF, by inducing production of IFN-gamma and TNF-alpha, two cytokines with synergistic inhibitory effects on hematopoietic colony formation. Because cell types that are able to produce NKSF/IL-12 are present in normal bone marrow and NKSF/IL-12 production in vivo and can be stimulated during bacterial or parasitic infection, it is possible that the direct stimulatory effect of NKSF/IL-12 on hematopoietic progenitor cells and the indirect inhibitory effect mediated by secondary cytokine production by lymphoid cells may play a role in the regulation of physiologic hematopoiesis and in its alterations during infection.
NK细胞刺激因子，即白细胞介素-12（NKSF/IL-12），是一种由单核巨噬细胞、B细胞以及可能的其他辅助细胞类型产生的异二聚体细胞因子。尽管已证实NKSF/IL-12对成熟T细胞和NK细胞具有主要生物学效应，可诱导细胞因子分泌、增强细胞毒性并促进增殖，但最近在小鼠系统中的证据表明，NKSF/IL-12可能在早期淋巴细胞造血祖细胞和胸腺细胞的分化中发挥作用。在本文中，我们分析了重组人NKSF/IL-12对来自人外周血和骨髓的高度富集的造血祖细胞形成集落的影响。在1至10 ng/ml的浓度下，NKSF/IL-12与干细胞因子和白细胞介素-3协同作用，诱导混合集落、红系集落和髓系集落的形成。因此，人NKSF/IL-12与小鼠NKSF/IL-12一样，似乎属于一小类早期起作用的细胞因子，包括白细胞介素-6、粒细胞集落刺激因子、白血病抑制因子和白细胞介素-11，它们能够与干细胞因子和白细胞介素-3协同作用，诱导极早期造血祖细胞的增殖和分化。然而，在与祖细胞一起培养的NK细胞富集制剂存在的情况下，NKSF/IL-12通过诱导干扰素-γ和肿瘤坏死因子-α的产生，抑制由白细胞介素-3和粒细胞巨噬细胞集落刺激因子支持形成的造血集落，这两种细胞因子对造血集落形成具有协同抑制作用。由于能够产生NKSF/IL-12的细胞类型存在于正常骨髓中，且体内可产生NKSF/IL-12，并且在细菌或寄生虫感染期间可被刺激，因此NKSF/IL-12对造血祖细胞的直接刺激作用以及淋巴细胞产生的次级细胞因子介导的间接抑制作用可能在生理性造血的调节及其在感染期间的改变中发挥作用。
