Potential mechanisms relating infection and GVL effects. GVL activity prevents hematologic malignant disease relapse following allogeneic SCT. In this regard, mechanisms for how viral infections like CMV might actually interact with leukemia relapse remain unknown, but numerous effects of CMV on the human immune system have been described. CMV is a lytic infection and has a direct cytopathic effect. CMV has immunosuppressive effects by itself, demonstrated by an increase of other infections associated with CMV reactivation. CMV is a potent activator of the first-line defense and may induce expansion in mature natural killer (NK) cells and γδT cells cross-reactive to CMV and leukemia cells. In humans, CMV persists in antigen-presenting cells (APCs) and could therefore take over the control of the adaptive immune response. Because pp65 as the most immune-dominant antigen can induce strong T-cell responses, efficient host protection as well as immunopathology may be due to the adaptive T-cell response against CMV. However, due to the strong and persistent T-cell stimulation, T-cell exhaustion and senescence may be an issue, especially in the elderly patient. MHC, major histocompatibility complex; TCR, T-cell receptor.