Unique human immune signature of Ebola virus disease in Guinea

作者：Ruibal Paula; Oestereich Lisa; Luedtke Anja; Becker Ziaja Beate; Wozniak David M; Kerber Romy; Korva Misa; Cabeza Cabrerizo Mar; Bore Joseph A; Koundouno Fara Raymond; Duraffour Sophie; Weller Romy; Thorenz Anja; Cimini Eleonora; Viola Domenico; Agrati Chiara; Repits Johanna; Afrough Babak; Cowley Lauren A; Ngabo Didier; Hinzmann Julia; Mertens Marc; Vitoriano Ines; Logue Christopher H; Boettcher Jan Peter; Pallasch Elisa; Sachse Andreas; Bah Amadou

来源：Nature, 2016, 533(7601): 100-+.

DOI：10.1038/nature17949

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 virus(2,3). 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.

• 出版日期2016-5-5