Systemic immunostimulatory therapies, such as high-dose (HD) IL-2 administration in both mice and humans as well as acute inflammation that occurs after acute viral infections, can induce robust bystander T cell activation, overcoming a lack of CD25 expression on memory T cells not undergoing TCR signaling yet allowing for effector functions such as NKG2D-mediated lysis of tumor or virally infected cells. Here, KLRK1 is linked to viral infectious disease.