학술논문
Avatar Mice Underscore the Role of the T Cell-Dendritic Cell Crosstalk in Ebola Virus Disease and Reveal Mechanisms of Protection in Survivors.
Document Type
Article
Author
Rottstegge, Monika; Tipton, Tom; Oestereich, Lisa; Ruibal, Paula; Nelson, Emily V.; Olal, Catherine; Port, Julia R.; Seibel, Johan; Pallasch, Elisa; Bockholt, Sabrina; Koundouno, Fara Raymond; Boré, Joseph Akoi; Rodríguez, Estefanía; Escudero-Pérez, Beatriz; Günther, Stephan; Carroll, Miles W.; Muñoz-Fontela, César
Source
Subject
*EBOLA virus disease
*T cell receptors
*ANTIGEN presenting cells
*EBOLA virus
*MAJOR histocompatibility complex
*T cells
*MULTIPLE organ failure
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Language
ISSN
0022-538X
Abstract
Ebola virus disease (EVD) is a complex infectious disease characterized by high inflammation, multiorgan failure, the dysregulation of innate and adaptive immune responses, and coagulation abnormalities. Evidence accumulated over the last 2 decades indicates that, during fatal EVD, the infection of antigen-presenting cells (APC) and the dysregulation of T cell immunity preclude a successful transition between innate and adaptive immunity, which constitutes a key disease checkpoint. In order to better understand the contribution of the APC-T cell crosstalk to EVD pathophysiology, we have developed avatar mice transplanted with human, donorspecific APCs and T cells. Here, we show that the transplantation of T cells and APCs from Ebola virus (EBOV)-naive individuals into avatar mice results in severe disease and death and that this phenotype is dependent on T cell receptor (TCR)-major histocompatibility complex (MCH) recognition. Conversely, avatar mice were rescued from death induced by EBOV infection after the transplantation of both T cells and plasma from EVD survivors. These results strongly suggest that protection from EBOV reinfection requires both cellular and humoral immune memory responses. [ABSTRACT FROM AUTHOR]