Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD1. In particular, very little is known about human immune responses to Ebola virus2,3. Here we evaluate the physiology of the human T cell immune response in EVD patients at the time of admission to the Ebola Treatment Center in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we identify an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by a high percentage of CD4+ and CD8+ T cells expressing the inhibitory molecules CTLA-4 and PD-1, which correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation, despite comparable overall T cell activation. Concomitant with virus clearance, survivors mounted a robust Ebola-virus-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.
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We thank the African Union, MSF and WHO field teams and the Guinean health authorities in Guéckédou, Coyah and Conakry for their commitment and cooperation. We also thank J. Snyder-Cappione (Boston University) and M. Altfeld (Heinrich Pette Institute) for technical support. The EMLab is a technical partner of the WHO Emerging and Dangerous Pathogens Laboratory Network (EDPLN), and the Global Outbreak Alert and Response Network (GOARN) and the deployments in West Africa have been coordinated and supported by the GOARN Operational Support Team at WHO/HQ. This work was carried out in the context of the project EVIDENT (Ebola virus disease: correlates of protection, determinants of outcome, and clinical management) that received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 666100 and in the context of service contract IFS/2011/272-372 funded by Directorate-General for International Cooperation and Development. The project was further supported by grant GU 883/4-1 from the German Research Foundation. This project has been funded in in part with funds from the Spanish National Plan for Research and Development ISCIII and FEDER RD12/0018/006 as well as federal funds from the Frederick National Laboratory for Cancer Research, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This research was supported in part by the Intramural Research Program of the NIH, Frederick National Laboratory, Center for Cancer Research. A.L. is a recipient of a pre-doctoral fellowship from the Leibniz Center of Infection. Z.K. is a recipient of a fellowship from the European Program for Public Health Microbiology Training (EUPHEM).