Douay L, Giarratana M C, Mary J Y, Gorin N C
Unité de Recherche sur Les Greffes de Cellules Souches Hématopoïétiques, CHU Saint-Antoine, Paris, France.
Br J Haematol. 1994 Mar;86(3):475-82. doi: 10.1111/j.1365-2141.1994.tb04776.x.
IL2 infusion may benefit patients with haematological malignancies by lowering the disease burden. However, conflicting data have been reported on IL2 effects on myelopoiesis, in vitro as well as in vivo. In the present study we investigated the ability of IL2 to act on committed and primitive bone marrow progenitor cells in defined serum-free (SF) culture conditions which avoid many technical biases such as interference by exogenous stimulating or inhibiting factors. Low doses of IL2 (0.1-1000 U/ml) were studied without or in combination with recombinant IL3, GM-CSF and erythropoietin, in SF long-term marrow culture (LTMC). We report data in favour of an inhibitory activity of IL2 limited to committed progenitors and excluding more primitive haemopoietic stem cells, as shown by an alteration of CFU-GM proliferation during the first 5 weeks of LTMC, decreasing with time, unaffected BFU-E and increased nucleated cell production. Beyond week 5, no difference was observed between IL2 supplemented cultures and the SF control cultures. In parallel, IL2 induced the adherence of fibroblastic cells and their progeny. In addition to the inhibitory effect, IL2 appeared to limit the stimulating effect on granulopoiesis and erythropoiesis of myeloid growth factors (GF) such as combination of IL3, GM-CSF and EPO. Indeed, in SF-LTMC conditions, IL2 inhibitory effect is effective on CFU-GM production throughout the 7 weeks of LTMC and on BFU-E during the first 2 weeks only. These data confirm the interaction of IL2 with other GFs in the complex interplay of the cytokine network.
输注白细胞介素-2（IL2）可能通过降低疾病负担使血液系统恶性肿瘤患者受益。然而，关于IL2在体外和体内对骨髓生成的影响，已有相互矛盾的数据报道。在本研究中，我们研究了在无血清（SF）的特定培养条件下，IL2作用于定向和原始骨髓祖细胞的能力，这种条件避免了许多技术偏差，如外源性刺激或抑制因子的干扰。在SF长期骨髓培养（LTMC）中，研究了低剂量IL2（0.1 - 1000 U/ml）单独或与重组IL3、粒细胞-巨噬细胞集落刺激因子（GM-CSF）和促红细胞生成素联合使用的情况。我们报告的数据表明，IL2的抑制活性仅限于定向祖细胞，不影响更原始的造血干细胞，这表现为在LTMC的前5周内集落形成单位-粒细胞-巨噬细胞（CFU-GM）增殖改变，随时间减少，爆式红系集落形成单位（BFU-E）不受影响，有核细胞生成增加。在第5周之后，添加IL2的培养物与SF对照培养物之间未观察到差异。同时，IL2诱导成纤维细胞及其后代的黏附。除了抑制作用外，IL2似乎还限制了骨髓生长因子（GF）如IL3、GM-CSF和促红细胞生成素（EPO）联合使用对粒细胞生成和红细胞生成的刺激作用。实际上，在SF-LTMC条件下，IL2的抑制作用在LTMC的整个7周内对CFU-GM产生有效，仅在最初2周内对BFU-E有效。这些数据证实了IL2在细胞因子网络复杂相互作用中与其他GF的相互作用。
