Hepatitis B Virus-Specific Cellular Immunity Contributes to the Outcome of Occult Hepatitis B Virus Infection
Weiyun Zhang, Shengxue Luo, Tingting Li, Min Wang, Jieting Huang, Qiao Liao, Bochao Liu, Rong Xia, Linhai Li, Jean‐Pierre Allain, Yongshui Fu, Chengyao Li
Abstract
There is little known of immunologic factors leading to the occurrence of occult HBV infection (OBI). Specific cellular immune response to hepatitis B virus (HBV) core/pol peptides was compared between blood donor populations, including 37 OBIs, 53 chronic HBV infections (CHB), 47 resolved infections, and 56 non-infected controls, respectively. The rate of CD4 + /CD8 + T cell proliferation in OBI or CHB carriers was higher than in HBV resolved and non-infected individuals ( P < 0.05). The intensity of IFN-γ-secretion T-cell response of OBI carriers was highest, followed by CHB and resolved infections, and non-infected individuals ( P < 0.05). The frequency of intracellular IFN-γ and IL-17A CD4 + /CD8 + and IL-21 CD4 + T-cell responses was significantly higher in resolved infections than in OBI or CHB carriers ( P < 0.05), while the level of extracellular IL-17A of peripheral blood mononuclear cells (PBMCs) was higher in OBI and CHB carriers than in resolved infections ( P < 0.01). The frequency of intracellular IL-10 CD4 + T-cell response in CHB, OBI, and resolved infections was higher than in HBV non-infected individuals ( P < 0.01). Intracellular IL-10 CD8 + T cell and extracellular IL-10 T-cell responses were higher in CHB than in OBI ( P = 0.012) or HBV resolved infections ( P < 0.01). In conclusion, the higher level of effective T-cell response with IFN-γ, IL-17A, and IL-21 contributes to resolved infection outcome, while higher levels of suppressive T-cell response with IL-10 result in HBV chronicity. OBI is an intermediary status between HBV resolved and chronic infections, in which IL-21 effector and IL-10 suppressor T-cell responses play an important role in directing the outcome of HBV infection.