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Received Mar 2, 2018; Accepted Apr 5, 2018
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1. Introduction
Severe aplastic anemia (SAA) is characterized by severe pancytopenia, failure of hematopoietic function, an acute onset, rapid progression, and a high fatality rate [1]. SAA is an autoimmune disease whose immunotolerance mechanism has been shown to be broken and mediated by hyperfunctional T lymphocytes. Proliferation and over activation of cytotoxic T lymphocytes (CTLs; CD8+ T cells) are the direct causes of bone marrow failure in patients with SAA [2]. Our group conducted a series of studies in which we found abnormal expression of various immunomodulatory molecules on the surface of CTLs and an increased number of activated effective T cells (CD8+ human leukocyte antigen D related + T cells), with obviously higher levels of intracellular molecules, including perforin, granzyme B, tumor necrosis factor (TNF) β, and FasL, which confirmed that CTLs may be key cells in the pathogenesis of SAA [3–5]. A variety of viruses are known to lead to hyperfunction of CTLs via disruption of the immune balance and ultimately contribute to the occurrence of SAA. Hepatitis B is the most common of these viruses [6].
Epstein Barr virus (EBV) is a type of human T-lymphotropic double-stranded DNA virus that belongs to the herpes virus family, which was first isolated from African children with Burkitt lymphoma in 1964 by Epstein et al. [7]. EBV has a dual infection strategy: lytic infection and latent infection [8]. The CTLs’ response plays an important role in fighting EBV infection, especially in persistent virus infection. In early stages of infectious mononucleosis, the non-EBV-specific CTLs in the peripheral blood are activated and play a part in the nonspecific immune attack. The infectious bodies then produce EBV-specific active CTLs, inhibiting the proliferation of EBV infected cells and preventing the recurrence of this infection [9]. EBNA-1 is a kind of nucleoprotein encoded by the BKRF1 genome. EBV has various stages of latency with varying viral gene expression, and EBNA1 is expressed during most of these stages. It can combine with the replication origin of EBV (oriP), which further plays a...