In summary, HBV-specific IFN-γ, IL-17A, and IL-21 secretion CD4+/CD8+ effector T-cell responses contributed to the resolution of viral infection, while IL-10 secretion CD4+/CD8+ T-cell responses contributed to progression to chronicity in the natural history of HBV infection, during which IL-21 and IL-10 T-cell responses played critical roles in the spontaneous resolution of HBV infection. This evidence concerns the gene CD4 and viral infectious disease.