Mucosal infections are prevented by a specialized local immune system. Immune cells of this compartment can also be found in the blood and are characterized by the expression of mucosa-specific homing molecules. Here, the cellular immune responses after inactivated poliovirus immunization (IPV) in poliovirus orally pre-immunized donors were investigated. Subcutaneous IPV induced a transient increase in the proliferative response against poliovirus antigen and in the number of poliovirus-specific CD4(+) T cells in the blood of the vaccinees. These cells were characterized to be of the effector memory type (CD45RA(-)/CD45RO(+)/CCR7(-)/CD27(+)) and expressed the homing molecule alpha(4)beta(7), indicating their origin from the gut. Together these data show the recurrence of gut-derived poliovirus-specific cells upon IPV and evaluate the whole-blood assay as a powerful tool for monitoring the success of a vaccination.