Fu et al. analyze Bcl6fl/flFoxp3Cre/Cre mice and show that Tfr deficiency enhances immunity to influenza virus but promotes autoimmunity, which sheds new light on the understanding and treatment of autoimmune diseases.

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The majority of hepatitis C virus (HCV) infection develops chronic infection, which causes steatosis, cirrhosis and hepatocellular carcinoma. However, understanding HCV chronicity and pathogenesis is hampered by its narrow host range, mostly restricted to human and chimpanzee. Recent endeavour to infect a variety of humanized mice has not been able to achieve persistent HCV infection unless the essential innate immune responsive genes are knocked out. Nevertheless, such immune-compromised humanized mice still lacked HCV infection-induced hepatopathogenesis. Here we report that transgenic mice in ICR background harboring both human CD81 and occludin genes (C/OTg) are permissive to HCV infection at a chronicity rate comparable to humans. In this mouse model, HCV accomplishes its replication cycle, leading to sustained viremia and infectivity for more than 12 months post infection with expected fibrotic and cirrhotic progression. Host factors favorable for HCV replication, and inadequate innate immune-response may contribute to the persistence. Lastly, NS3/4 protease inhibitor telaprevir can effectively inhibit de novo RNA synthesis and acute HCV infection of C/OTg mice. Thus, chronic HCV infection with complete replication cycle and hepatopathologic manifestations is recapitulated, for the first time, in immune-competent mice. This model will open a new venue to study the mechanisms of chronic hepatitis C and develop better treatments.

Network-based analysis of transcriptome dynamics during activation in two human T-cell subpopulations identifies key regulators, and reveals that PLAU plays a critical role in both human and murine regulatory T-cell function.

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Macrophage infiltration and activation in myocardium are hallmarks of acute cardiac inflammatory response to high blood pressure. However, the underlying mechanisms remain elusive. In this article, we report that CD8+ T cells are required for cardiac recruitment and activation of macrophages. First, mice with CD8 gene-targeted (CD8 knockout) or CD8+ T cells depleted by Ab showed significantly reduced cardiac inflammatory response to the elevation of blood pressure after angiotensin II (Ang II) infusion, whereas CD8 knockout mice reconstituted with CD8+ T cells restored the sensitivity to Ang II. More importantly, CD8+ T cells were required for macrophage infiltration in myocardium and subsequent activation to express proinflammatory cytokines and chemokines. Furthermore, macrophage activation required direct contact with activated CD8+ T cells, but with TCR dispensable. TCR-independent activation of macrophages was further confirmed in MHC class I–restricted OVA-specific TCR transgenic mice, which showed a CD8+ T cell activation and cardiac proinflammatory response to Ang II similar to that of wild-type mice. Finally, only myocardium-infiltrated, but not peripheral, CD8+ T cells were specifically activated by Ang II, possibly by the cardiac IFN-γ that drove IFN-γR+ CD8+ T cell infiltration and activation. Thus, this work identified a TCR-independent innate nature of CD8+ T cells that was critical in initiating the sterile immune response to acute elevation of blood pressure.