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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 EVD. In particular, very little is known about human immune responses to Ebola virus. 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.

Original publication

DOI

10.1038/nature17949

Type

Journal article

Journal

Nature

Publication Date

05/2016

Volume

533

Pages

100 - 104

Addresses

Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany.

Keywords

T-Lymphocytes, Humans, Hemorrhagic Fever, Ebola, Inflammation Mediators, Patient Discharge, Flow Cytometry, Viral Load, Longitudinal Studies, Lymphocyte Activation, Survivors, Guinea, Female, Male, Ebolavirus, CTLA-4 Antigen, Programmed Cell Death 1 Receptor