Functional CD8+ T Cell Responses in Lethal Ebola Virus Infection.

摘要

Ebolavirus (EBOV) causes highly lethal hemorrhagic fever that leads to death in up to 90% of infected humans. EBOV infection induces massive lymphocyte apoptosis, which is thought to prevent a functional adaptive immune response. In addition, in vitro studies show that EBOV induces aberrant responses in dendritic cells, which is thought to contribute to a failed adaptive immune response. In this study we show that in a lethal mouse model of EBOV infection there is an increase in expression of the activation marker CD44 in CD4+ and CD8+ T cells late in infection. This precedes a dramatic rebound of lymphocyte numbers in the blood. Surprisingly, adoptive transfer of splenocytes from moribund infected animals protected na ve animals from EBOV but not marburgvirus (MARV) challenge. In addition, we observed EBOV-specific CD8+ T cell responses in moribund EBOV-infected mice, and adoptive transfer of these cells alone could transfer protection to EBOV-challenged na ve mice. Therefore, despite significant lymphocyte apoptosis, a functional and specific adaptive immune response is made in lethal EBOV infection. This data suggests that anti- EBOV therapeutics may curtail the progression of the disease long enough to allow the adaptive immune response to respond and minimize or obvert pathology.