赵金存教授及其合作团队,通过在小鼠肺气道中开展的实验,发现记忆性CD4+ T细胞(Airway memory CD4+ T cell)能间接起到清除病毒的作用。在病毒感染后,记忆性CD4+ T细胞能第一时间分泌γ干扰素。γ干扰素激活抗病毒天然免疫应答和增强抗病毒CD8+ T细胞免疫反应,从而有效清除病毒感染细胞。更为重要的是,此CD4+ T细胞可诱导产生同时针对MERS和SARS冠状病毒的T细胞免疫应答。(广州日报)作者: ipsvirus 时间: 2016-6-22 18:38 Airway Memory CD4+ T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses
Jincun Zhao6,correspondenceemail, Jingxian Zhao6, Ashutosh K. Mangalam, Rudragouda Channappanavar, Craig Fett, David K. Meyerholz, Sudhakar Agnihothram7, Ralph S. Baric, Chella S. David, Stanley Perlman
Highlights
•Intranasal but not subcutaneous vaccination protects mice from pathogenic human CoVs
•Protection is mediated by airway memory CD4+ T cells
•IFN-γ produced by airway memory CD4+ T cells is required for protection
•A conserved epitope in SARS-CoV and MERS-CoV induces cross-reactive T cell responses
Summary
Two zoonotic coronaviruses (CoVs)—SARS-CoV and MERS-CoV—have crossed species to cause severe human respiratory disease. Here, we showed that induction of airway memory CD4+ T cells specific for a conserved epitope shared by SARS-CoV and MERS-CoV is a potential strategy for developing pan-coronavirus vaccines. Airway memory CD4+ T cells differed phenotypically and functionally from lung-derived cells and were crucial for protection against both CoVs in mice. Protection was dependent on interferon-γ and required early induction of robust innate and virus-specific CD8+ T cell responses. The conserved epitope was also recognized in SARS-CoV- and MERS-CoV-infected human leukocyte antigen DR2 and DR3 transgenic mice, indicating potential relevance in human populations. Additionally, this epitope was cross-protective between human and bat CoVs, the progenitors for many human CoVs. Vaccine strategies that induce airway memory CD4+ T cells targeting conserved epitopes might have broad applicability in the context of new CoVs and other respiratory virus outbreaks.