CD28 and B-cell chronic lymphocytic leukemia: Based on expression of extracellular surface markers (CD45RA, CCR7, CD27 and CD28), EBV-specific CD8+ T cells of CLL patients displayed an advanced differentiation state compared to HC-derived T cells, with a significant decrease in cells with an early effector memory phenotype and an increase in more differentiated effector populations (Fig. 2A).