T-Cell Receptor Diversity and the Control of T-Cell Homeostasis Mark Ebola Virus Disease Survival in Humans. (6th July 2018)

• Record Type: Journal Article
• Authors: Speranza, Emily; Ruibal, Paula; Port, Julia R; Feng, Feng; Burkhardt, Lia; Grundhoff, Adam; Günther, Stephan; Oestereich, Lisa; Hiscox, Julian A; Connor, John H; Muñoz-Fontela, César
• Is Part Of: Journal of infectious diseases. Volume 218(2018)Supplement 5
• Page Start: S508
• Page End: S518
• Publication Date: 2018-07-06
• Subjects: Ebola virus -- gene expression -- T cells -- T-cell receptor; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiy352
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Differences in T-cell phenotype, particularly the expression of markers of T-cell homeostasis, have been observed in fatal and nonfatal Ebola virus disease (EVD). However, the relationship between these markers with T-cell function and virus clearance during EVD is poorly understood. To gain biological insight into the role of T cells during EVD, combined transcriptomics and T-cell receptor sequencing was used to profile blood samples from fatal and nonfatal EVD patients from the recent West African EVD epidemic. Fatal EVD was characterized by strong T-cell activation and increased abundance of T-cell inhibitory molecules. However, the early T-cell response was oligoclonal and did not result in viral clearance. In contrast, survivors mounted highly diverse T-cell responses, maintained low levels of T-cell inhibitors, and cleared Ebola virus. Our findings highlight the importance of T-cell immunity in surviving EVD and strengthen the foundation for further research on targeting of the dendritic cell-T cell interface for postexposure immunotherapy.