Cytotoxic T cell responses to AAV capsid were described for the first time in a clinical trial for Hemophilia B, where the loss of transgene expression was correlated with a transient and asymptomatic elevation of liver transaminases and interferon-γ (IFN-γ) release from peripheral blood mononuclear cells (PBMCs), as detected by IFN-γ enzyme-linked immunospot (ELISpot). This evidence concerns the gene IFNG and hemophilia B.