Dynamic changes in the immunological characteristics of T lymphocytes in surviving patients with severe fever with thrombocytopenia syndrome (SFTS)

Objective: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality. T cell deficiency has recently been described, but the changes in T cell functionality during acute SFTS virus (SFTSV) infection and the mechanisms leading to T lymphocyte death remain largely unknown. This study was conducted to evaluate T cell functionality and the expression of apoptotic/proliferation and activation/inhibition markers during acute SFTSV infection. Methods: Twenty-eight surviving SFTS patients were sequentially sampled during their entire hospital stay. SFTSV RNA copies were investigated using real-time RT-PCR. The expression levels of apoptotic markers (annexin V and CD95) and proliferation and activation markers (Ki-67, HLA-DR, and CD25) and the expression levels of programmed cell death-1 (PD-1), interferon gamma (IFN-γ), and granzyme B in T cells were evaluated by flow cytometry for the SFTS patients. Results: In parallel with T cell depletion, higher annexin V and CD95 expression was observed in SFTS patients. Additionally, the expression levels of Ki-67, HLA-DR, CD25, and PD-1 and the levels of IFN-γ and granzyme B in T lymphocytes were markedly increased in the SFTS patients. Conclusions: T cell proliferation, activation, and functional enhancement were apparent despite the observation of T cell apoptosis, suggesting that these processes are involved in the complex protective response to SFTSV infection. Keywords: Severe fever with thrombocytopenia syndrome, T lymphocytes, Apoptosis, T cell proliferation, T cell activation, PD-1, T cell functionalit