意大利圣拉斐尔生命健康大学Matteo Iannacone团队发现，一种库普弗细胞亚群能够逆转肝细胞诱导的T细胞功能障碍。相关论文于2021年8月31日在线发表于国际学术期刊《免疫》。

研究人员使用了一个乙肝病毒（HBV）感染的小鼠模型，其中HBV特异性的初始CD8⁺ T细胞能够识别肝细胞抗原，并会产生一种免疫功能紊乱的状态，通过这个模型研究人员鉴定了库普弗细胞（KC）的一个亚群（称为KC2），在白细胞介素-2（IL-2）给药后交叉呈递肝细胞抗原，从而改善T细胞的抗病毒功能。从所有KC（包括KC2）中去除MHC-I，或选择性地耗尽KC2，都会损害IL-2逆转肝内活化诱发T细胞功能障碍的能力。总之，通过感知IL-2和交叉呈递肝细胞抗原，KC2克服了肝脏微环境的耐受性潜力，并提示了增强肝脏T细胞免疫的新策略。

据介绍，KC是高度丰富的、血管内的、驻留肝脏的巨噬细胞，并以其清道夫和吞噬功能而闻名。KC也可以向CD8⁺ T细胞提供抗原，并促进耐受性或效应分化，但对这些不同结果的机制还不甚了解。

附：英文原文

Title: Identification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by hepatocellular priming

Author: Giorgia De Simone, Francesco Andreata, Camille Bleriot, Valeria Fumagalli, Chiara Laura, José M. Garcia-Manteiga, Pietro Di Lucia, Stefano Gilotto, Xenia Ficht, Federico F. De Ponti, Elisa B. Bono, Leonardo Giustini, Gioia Ambrosi, Marta Mainetti, Paola Zordan, Alexandre P. Bénéchet, Micol Ravà, Svetoslav Chakarov, Federica Moalli, Marc Bajenoff, Luca G. Guidotti, Florent Ginhoux, Matteo Iannacone

Issue&Volume: 2021-08-31

Abstract: Kupffer cells (KCs) are highly abundant, intravascular, liver-resident macrophages known for their scavenger and phagocytic functions. KCs can also present antigens to CD8+ T cells and promote either tolerance or effector differentiation, but the mechanisms underlying these discrepant outcomes are poorly understood. Here, we used a mouse model of hepatitis B virus (HBV) infection, in which HBV-specific naive CD8+ T cells recognizing hepatocellular antigens are driven into a state of immune dysfunction, to identify a subset of KCs (referred to as KC2) that cross-presents hepatocellular antigens upon interleukin-2 (IL-2) administration, thus improving the antiviral function of T cells. Removing MHC-I from all KCs, including KC2, or selectively depleting KC2 impaired the capacity of IL-2 to revert the T cell dysfunction induced by intrahepatic priming. In summary, by sensing IL-2 and cross-presenting hepatocellular antigens, KC2 overcome the tolerogenic potential of the hepatic microenvironment, suggesting new strategies for boosting hepatic T cell immunity.

DOI: 10.1016/j.immuni.2021.05.005

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00211-9