Lagneaux L, Delforge A, Bron D, Massy M, Bernier M, Stryckmans P
Service de Médecine Interne et Laboratoire d'Investigation Clinique Henri Tagnon, Institut J. Bordet, Brussels, Belgium.
Br J Haematol. 1997 Jun;97(3):612-20. doi: 10.1046/j.1365-2141.1997.792715.x.
We investigated the potential role of transforming growth factor-beta (TGF-beta) on spontaneous and cytokine-induced proliferation of B-cell chronic lymphocytic leukaemia (B-CLL) cells in vitro. Purified B lymphocytes from 21 B-CLL patients were cultured for 5 d in the presence of medium alone, IL-2 and/or IL-10, in the presence or absence of TGF-beta, and proliferation was measured by 3H-thymidine incorporation. TGF-beta inhibited B-cell proliferation in the majority of patients (15/21) but no inhibition was detected in 6/21 patients whatever the type of stimulant used. Addition of neutralizing antibodies to TGF-beta increased spontaneous and cytokine-induced proliferation; this effect was dose dependent and specific because addition of an irrelevant chicken IgG had no effect on B-CLL proliferation. In resistant patients, neutralizing antibodies to TGF-beta did not increase the proliferation. The expression of TGF-beta receptors on B-CLL cells was significantly lower than the one observed on normal CD5+ B lymphocytes for which the sensitivity to TGF-beta inhibition was more marked than in CLL. In addition, we found a strong correlation between the response of leukaemic B cells to TGF-beta inhibitory action and the expression of TGF-beta receptors on these cells. In summary, TGF-beta appears to function in CLL as a negative regulator of B lymphocytes but loss of responsiveness to this factor accompanied by a decrease of TGF-beta receptor expression, might provide a selective advantage to B-CLL lymphocytes.
我们研究了转化生长因子-β（TGF-β）在体外对B细胞慢性淋巴细胞白血病（B-CLL）细胞自发增殖及细胞因子诱导增殖的潜在作用。从21例B-CLL患者中纯化的B淋巴细胞在单独培养基、白细胞介素-2（IL-2）和/或白细胞介素-10存在或不存在、以及存在或不存在TGF-β的情况下培养5天，通过³H-胸腺嘧啶核苷掺入法测量增殖情况。TGF-β抑制了大多数患者（15/21）的B细胞增殖，但无论使用何种刺激剂，在6/21例患者中均未检测到抑制作用。添加TGF-β中和抗体可增加自发增殖及细胞因子诱导的增殖；这种效应呈剂量依赖性且具有特异性，因为添加无关的鸡IgG对B-CLL增殖无影响。在耐药患者中，TGF-β中和抗体并未增加增殖。B-CLL细胞上TGF-β受体的表达明显低于正常CD5⁺ B淋巴细胞，正常CD5⁺ B淋巴细胞对TGF-β抑制的敏感性比CLL更明显。此外，我们发现白血病B细胞对TGF-β抑制作用的反应与这些细胞上TGF-β受体的表达之间存在强烈相关性。总之，TGF-β在CLL中似乎作为B淋巴细胞的负调节因子发挥作用，但对该因子反应性的丧失伴随着TGF-β受体表达的降低，可能为B-CLL淋巴细胞提供选择性优势。
