Ebola-Specific CD8+ and CD4+ T-Cell Responses in Sierra Leonean Ebola Virus Survivors With or Without Post-Ebola Sequelae
Stephanie M. LaVergne, Saori Sakabe, Lansana Kanneh, Mambu Momoh, Foday Al-Hassan, Mohamed Yilah, Augustine Goba, John Demby Sandi, Michael Gbakie, Beatrice Cubitt, Matthew L. Boisen, Jessica Mayeux, Ashley R. Smira, Kayla R Shore, Iris Bica, K. Michael Pollard, Juan Carlos de la Torre, Luis M. Branco, Robert F. Garry, Donald S. Grant, John S. Schieffelin, Michael B. A. Oldstone, Brian M. Sullivan
Abstract
BACKGROUND: Ebola virus (EBOV) disease has killed thousands of West and Central Africans over the past several decades. Many who survive the acute disease later experience post-Ebola syndrome, a constellation of symptoms whose causative pathogenesis is unclear. METHODS: We investigated EBOV-specific CD8+ and CD4+ T-cell responses in 37 Sierra Leonean EBOV disease survivors with (n = 19) or without (n = 18) sequelae of arthralgia and ocular symptoms. Peripheral blood mononuclear cells were infected with recombinant vesicular stomatitis virus encoding EBOV antigens. We also studied the presence of EBOV-specific immunoglobulin G, antinuclear antibodies, anti-cyclic citrullinated peptide antibodies, rheumatoid factor, complement levels, and cytokine levels in these 2 groups. RESULTS: Survivors with sequelae had a significantly higher EBOV-specific CD8+ and CD4+ T-cell response. No differences in EBOV-specific immunoglobulin G, antinuclear antibody, or anti-cyclic citrullinated peptide antibody levels were found. Survivors with sequelae showed significantly higher rheumatoid factor levels. CONCLUSION: EBOV-specific CD8+ and CD4+ T-cell responses were significantly higher in Ebola survivors with post-Ebola syndrome. These findings suggest that pathogenesis may occur as an immune-mediated disease via virus-specific T-cell immune response or that persistent antigen exposure leads to increased and sustained T-cell responses.