Previous studies have found that chronic hepatitis B virus (HBV) infection is associated with functionally-impaired virus-specific T cell responses. While, myeloid-derived suppressor cells (MDSCs) play a critical role in impairing antiviral T cell responses, the authors were interested in which viral factors are responsible for the expansion of MDSCs in chronic hepatitis B (CHB). The authors examined the circulating frequency of mMDSCs in 164 CHB patients and 70 healthy controls to examine this mechanism of monocytic MDSC (mMDSCs) expansion and T cell function suppression. The authors found that the proportion of mMDSCs in HBeAg-positive CHB patients was significantly higher compared with HBeAg-negative patients, and positively correlated with the level of HBeAg. Exposure of peripheral blood mononuclear cells (PBMCs) isolated from healthy donors to HBeAg was found to cause expansion of mMDSCs and significant upregulation of IL-1β, IL-6 and indoleamine-2,3-dioxygenase (IDO). Depletion of these cytokines stopped the HBeAg-induced mMDSCs expansion. In addition, HBeAg-induced mMDSCs were found to suppress autologous T cell proliferation in vitro, and the purified mMDSCs from HBeAg-positive patients reduced the proliferation of CD4+ and CD8+ T cells and IFN-γ production, all of which could be restored by inhibiting IDO. Therefore, HBeAg-induced mMDSC expansion impairs T cell function through the IDO pathway, leading to the establishment of a persistent HBV infection, and potentially, HBeAg-induced immune tolerance.
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