Young M R, Young M E, Wright M A
Department of Research Services, Hines V.A. Hospital, Illinois 60141.
Exp Hematol. 1990 Aug;18(7):806-11.
In previous studies, we demonstrated that immune-suppressive bone marrow cells appeared during a period of myelopoietic stimulation in mice bearing Lewis lung carcinoma (LLC) tumors and could be induced from normal bone marrow cells during 3 days of culture with supernatants of LLC variant cells. We have now shown that the capacity of LLC variants to induce immune suppressor cells was associated with the capacity to produce colony-stimulating factor (CSF) activities. The LLC variants that secreted more CSF activities also produced more bone marrow immune suppressor cell-inducing activity. The induction of immune-suppressive bone marrow cells was dependent on bone marrow cell proliferation because irradiation of bone marrow cells prior to culture with the CSF-containing supernatants blocked induction of suppressor cells. Culture supernatants of WEHI-3 cells and of pokeweed mitogen-stimulated spleen cells, rich sources of interleukin 3 (IL-3) and granulocyte-monocyte-CSF (GM-CSF), as well as recombinant mouse GM-CSF and recombinant mouse IL-3, also stimulated bone marrow suppressor cell activity. The combination of GM-CSF with IL-3 resulted in a synergistic rather than simply an additive induction of bone marrow suppressor cells. Conditioned medium of CSF-1-producing L cells did not induce bone marrow immune suppressor cells. These results suggest that during heightened periods of myelopoiesis, induction of bone marrow-derived immune suppressor cells may be stimulated by CSFs, such as by the singular or combined effects of GM-CSF and IL-3.
在先前的研究中，我们证明，在携带Lewis肺癌（LLC）肿瘤的小鼠骨髓造血刺激期会出现免疫抑制性骨髓细胞，并且在与LLC变异细胞的上清液共培养3天期间，这些细胞可从正常骨髓细胞诱导产生。我们现在已经表明，LLC变异体诱导免疫抑制细胞的能力与产生集落刺激因子（CSF）活性的能力相关。分泌更多CSF活性的LLC变异体也产生更多的骨髓免疫抑制细胞诱导活性。免疫抑制性骨髓细胞的诱导依赖于骨髓细胞增殖，因为在用含CSF的上清液培养之前对骨髓细胞进行照射可阻断抑制细胞的诱导。作为白细胞介素3（IL-3）和粒细胞-单核细胞集落刺激因子（GM-CSF）丰富来源的WEHI-3细胞以及商陆有丝分裂原刺激的脾细胞的培养上清液，以及重组小鼠GM-CSF和重组小鼠IL-3，也刺激了骨髓抑制细胞活性。GM-CSF与IL-3的组合导致骨髓抑制细胞的协同诱导而非简单的加性诱导。产生CSF-1的L细胞的条件培养基未诱导骨髓免疫抑制细胞。这些结果表明，在骨髓造血增强期，骨髓来源的免疫抑制细胞的诱导可能受到CSF的刺激，例如通过GM-CSF和IL-3的单一或联合作用。
