Galectin-1 (Gal-1) has been implicated in the progression of chronic lymphocytic leukemia (CLL) but also the development of immunodeficiency, which commonly accompany this malignancy. In this in vitro study, we investigated the effects of Gal-1 inhibition in the sera of immunocompromised CLL patients on immunomodulating properties of dendritic cells (DCs). DCs derived from peripheral blood mononuclear cells were treated with a healthy serum, CLL serum as well as the combination of CLL serum and Gal-1 inhibitor (OTX008). Following the treatment, the expression levels of DC maturation markers (CD80, CD83, CD86 and IDO-1) were determined as well as their cytokine profile and the ability to polarize the immune response in co-cultures with CD4+ T cells. After treatment with CLL serum, an increase in interleukin (IL)-10 production was observed in both DC cultures and co-cultures with CD4+ T cells. OTX008 caused a reduction in IL-10 production as well as IL-2, but no significant alteration in the expression of DC maturation markers or T regulatory cell (Treg) frequency was observed. The results of our study suggest that Gal-1 from CLL serum give rise to a specific IL-10+ CD4+ T cell phenotype, other than Treg, that could mediate immunodeficiency development in CLL patients.

中文翻译：

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galectin-1对慢性淋巴细胞白血病患者的免疫调节作用

Galectin-1（Gal-1）与慢性淋巴细胞性白血病（CLL）的发展有关，但也与免疫缺陷的发展有关，而免疫缺陷通常伴随着这种恶性肿瘤。在这个体外在这项研究中，我们研究了免疫受损的CLL患者血清中Gal-1抑制作用对树突状细胞（DC）免疫调节特性的影响。用健康血清，CLL血清以及CLL血清和Gal-1抑制剂（OTX008）的组合处理源自外周血单核细胞的DC。治疗后，测定DC成熟标志物（CD80，CD83，CD86和IDO-1）的表达水平，以及它们的细胞因子谱和在与CD4 + T细胞共培养中极化免疫应答的能力。用CLL血清处理后，在DC培养物中和与CD4 + T细胞的共培养物中均观察到白介素（IL）-10产生的增加。OTX008导致IL-10和IL-2的产生减少，但未观察到DC成熟标记物或T调节细胞（Treg）频率的表达发生明显变化。我们的研究结果表明，来自CLL血清的Gal-1会产生一种特定的IL-10 + CD4 + T细胞表型，而不是Treg，它可以介导CLL患者的免疫缺陷发展。