Although the determinants leading to polyfunctional cytokine expression in human virus-specific CD4+ T cells are unclear, the different IFN-γ expression patterns of virus-specific CD4+ T cells may reflect an influence of the amount and duration of antigen stimulation and/or extra inflammatory signals provided during viral infection that stimulate innate immune receptors, like TLRs which strongly promote acquisition of Th1 effector function [44, 45]. Here, IFNG is linked to viral infectious disease.