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半乳糖凝集素-1对慢性淋巴细胞白血病患者的免疫调节作用

Immunomodulatory effects of galectin-1 in patients with chronic lymphocytic leukemia.

作者信息

Kostic Milos, Dzopalic Tanja, Marjanovic Goran, Urosevic Ivana, Milosevic Ivana

机构信息

Department of Immunology, Medical Faculty of Nis, University of Nis, Nis, Serbia.

Department of Hematology and Clinical Immunology, Clinical Centre Nis, Nis, Serbia.

出版信息

Cent Eur J Immunol. 2021;46(1):54-62. doi: 10.5114/ceji.2021.105246. Epub 2021 Apr 18.

DOI:10.5114/ceji.2021.105246
PMID:33897284
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8056350/
Abstract

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.

摘要

半乳糖凝集素-1（Gal-1）与慢性淋巴细胞白血病（CLL）的进展有关，同时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。在这项体外研究中，我们调查了免疫功能低下的CLL患者血清中Gal-1抑制对树突状细胞（DC）免疫调节特性的影响。从外周血单核细胞衍生的DC用健康血清、CLL血清以及CLL血清与Gal-1抑制剂（OTX008）的组合进行处理。处理后，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反应的能力。用CLL血清处理后，在DC培养物和与CD4 T细胞的共培养物中均观察到白细胞介素（IL）-10产生增加。OTX008导致IL-10产生以及IL-2减少，但未观察到DC成熟标志物表达或调节性T细胞（Treg）频率的显著改变。我们的研究结果表明，CLL血清中的Gal-1会产生一种除Treg之外的特定IL-10 CD4 T细胞表型，该表型可能介导CLL患者免疫缺陷的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f78/8056350/37d2928d112c/CEJI-46-43813-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f78/8056350/75843e31b7a2/CEJI-46-43813-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f78/8056350/56926c9d33eb/CEJI-46-43813-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f78/8056350/37d2928d112c/CEJI-46-43813-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f78/8056350/f214b83eb816/CEJI-46-43813-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f78/8056350/61d9a701a53d/CEJI-46-43813-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f78/8056350/91eaba6c24bf/CEJI-46-43813-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f78/8056350/5e4537c7f12a/CEJI-46-43813-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f78/8056350/75843e31b7a2/CEJI-46-43813-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f78/8056350/56926c9d33eb/CEJI-46-43813-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f78/8056350/37d2928d112c/CEJI-46-43813-g007.jpg

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