奥地利科学院分子医学CeMM研究中心Andreas Bergthaler研究小组近日取得一项新成果。其最新研究探明了CD8⁺ T细胞在慢性病毒感染过程中诱导产生恶病质。2019年6月出版的《自然—免疫学》发表了这项成果。

课题组研究人员描述了慢性病毒感染小鼠可逆性恶病质模型，并鉴定了CD8阳性T细胞在IAC中的重要作用。与癌症相关的恶病质相关细胞因子不参与IAC。相反，病毒特异性CD8⁺T细胞引起脂肪组织的形态学和分子变化，导致脂质储存的减少。这些变化发生在CD⁺8T细胞反应峰值之前的一个时间点，需要T细胞固有的I型干扰素信号和抗原的特异性启动。研究结果将全身抗病毒免疫反应与脂肪组织重塑联系起来，揭示了CD8⁺T细胞在IAC中的未被重视的作用。

据介绍，恶病质是各种癌症、慢性炎症和感染的发病率和死亡率的主要原因。然而对引起恶病质机制的理解仍然有限，尤其是对感染相关恶病质（IAC）的理解。

附：英文原文

Title: CD8 + T cells induce cachexia during chronic viral infection

Author: Hatoon Baazim, Martina Schweiger, Michael Moschinger, Haifeng Xu, Thomas Scherer, Alexandra Popa, Suchira Gallage, Adnan Ali, Kseniya Khamina, Lindsay Kosack, Bojan Vilagos, Mark Smyth, Alexander Lercher, Joachim Friske, Doron Merkler, Alan Aderem, Thomas H. Helbich, Mathias Heikenwlder, Philipp A. Lang, Rudolf Zechner, Andreas Bergthaler

Issue&Volume: Volume 20 Issue 6, June 2019

Abstract: Cachexia represents a leading cause of morbidity and mortality in various cancers, chronic inflammation and infections. Understanding of the mechanisms that drive cachexia has remained limited, especially for infection-associated cachexia (IAC). In the present paper we describe a model of reversible cachexia in mice with chronic viral infection and identify an essential role for CD8+ T cells in IAC. Cytokines linked to cancer-associated cachexia did not contribute to IAC. Instead, virus-specific CD8+ T cells caused morphologic and molecular changes in the adipose tissue, which led to depletion of lipid stores. These changes occurred at a time point that preceded the peak of the CD8+ T cell response and required T cellintrinsic type I interferon signaling and antigen-specific priming. Our results link systemic antiviral immune responses to adipose-tissue remodeling and reveal an underappreciated role of CD8+ T cells in IAC.

DOI: 10.1038/s41590-019-0397-y

Source:https://www.nature.com/articles/s41590-019-0397-y