CD28 and viral infectious disease: CD4lowCD8high T cells have been studied in the context of various viral infections such as HHV-6 [34], EBV [35, 36] and CMV [36] and there is solid published evidence that stimulation of CD8+ T cells via their TCR in combination with CD28 costimulation, but none of those signals alone, can lead to de novo expression of CD4 [37–40].