Rodrigues Evandra Strazza, de Macedo Mayra Dorigan, Orellana Maristela Delgado, Takayanagui Osvaldo Massaiti, Palma Patrícia Vianna Bonini, Pinto Mariana Tomazini, de Oliveira Gislane Lelis Vilela, Malmegrim Kelen Cristina Ribeiro, Slavov Svetoslav Nanev, Covas Dimas Tadeu, Kashima Simone
1 Center for Cell-Based Research, Regional Blood Center of Ribeirão Preto, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, Brazil.
2 Department of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences of Ribeirão Preto, Ribeirão Preto, Brazil.
AIDS Res Hum Retroviruses. 2019 Feb;35(2):164-168. doi: 10.1089/AID.2018.0066. Epub 2018 Dec 22.
Human multipotent mesenchymal stromal cells (MSCs) display immunoregulatory functions that can modulate innate and adaptive cellular immune responses. The suppressive and immunomodulatory activities of MSCs occur through the action of soluble factors that are constitutively produced and released by these cells or, alternatively, after MSC induction by stimuli of inflammatory microenvironments. However, to date the contribution of MSCs in the inflammatory microenvironment resulting from viral infection is unknown. In our study, we evaluated the MSC immunosuppressive effect on human T lymphotropic virus type 1 (HTLV-1) infected T lymphocytes. To evaluate if MSC immunoregulation can influence the proliferation of HTLV-1 infected T lymphocytes, we compared the proliferation of lymphocytes obtained from HTLV-1 infected and healthy individuals cocultured in the presence of MSCs. It was observed that the lymphoproliferative inhibition by MSCs on infected lymphocytes was similar compared to the cells obtained from healthy individuals. In addition, this suppressive effect was related to a significant increase of indoleamine-2,3-dioxygenase and prostaglandin E2 gene expression (p ≤ .05). Furthermore, the HTLV-1 pol gene was less expressed after coculturing with MSCs, suggesting that the MSC immunoregulation can have effective suppression on HTLV-1 infected T cells. In conclusion, this study suggests that MSCs could be involved in the immunomodulation of the HTLV-1 infected T lymphocytes.
人多能间充质基质细胞(MSCs)具有免疫调节功能,可调节先天性和适应性细胞免疫反应。MSCs的抑制和免疫调节活性通过这些细胞组成性产生和释放的可溶性因子的作用发生,或者在炎症微环境刺激诱导MSCs后发生。然而,迄今为止,MSCs在病毒感染引起的炎症微环境中的作用尚不清楚。在我们的研究中,我们评估了MSCs对人1型嗜T淋巴细胞病毒(HTLV-1)感染的T淋巴细胞的免疫抑制作用。为了评估MSCs的免疫调节是否会影响HTLV-1感染的T淋巴细胞的增殖,我们比较了在MSCs存在下共培养的来自HTLV-1感染个体和健康个体的淋巴细胞的增殖情况。结果观察到,与从健康个体获得的细胞相比,MSCs对感染淋巴细胞的淋巴细胞增殖抑制作用相似。此外,这种抑制作用与吲哚胺-2,3-双加氧酶和前列腺素E2基因表达的显著增加有关(p≤0.05)。此外,与MSCs共培养后,HTLV-1 pol基因的表达较少,这表明MSCs的免疫调节可以对HTLV-1感染的T细胞产生有效的抑制作用。总之,本研究表明MSCs可能参与了HTLV-1感染的T淋巴细胞的免疫调节。