The role of T reg population in pathogenesis of Crimean Congo hemorrhagic fever

Abstract

Crimean-Congo hemorrhagic fever (CCHF) is a severe human infection caused by CCHF virus (CCHFV). Today, although the literature on CCHF pathogenesis is still limited, it is thought to be associated with immunosuppression in the early phase of infection followed by pro-inflammatory immune response that may lead to fatal outcomes. The aim of this study is to investigate the role of regulatory T-cells (T reg cells) in the pathogenesis of CCHFV. Peripheral blood mononuclear cell samples collected from 14 acute CCHF patients with mild disease course and 13 healthy subjects were included in this study. T reg expression and functional levels were analyzed by flow cytometry. T reg cells were identified as CD4+CD25 + CD127dim cells, and their functional levels were compared by measuring their ability to suppress CD69 and CD154 expression by activated T-cells. The flow cytometry analysis revealed that total T-cell and helper T-cell levels did not vary between the two groups. In contrast, CCHF patients displayed higher T reg cell levels but lower T reg suppressive activities when compared with control subjects. This is the first study on the involvement of T reg cells in CCHF pathogenesis. Our results indicate that even though T reg cell levels are elevated during acute phase of CCHF infection, not all generated T reg cells has immunosuppressive capacity, and therefore may not represent ‘true’ T reg cell population. Future studies on the intrinsic mechanisms responsible for the reduced T reg inhibitory activities are required for further enlightening the CCHF pathogenesis, especially in the acute phase of the disease. © 2018 Elsevier B.V.