Several reasons can be suggested for the intrinsic activation-induced lymphocyte depletion, such as i) canonical tumor antigen-specific activation by lymphoma cells, ii) cytokine-dependent bystander activation caused by DLBCL-secreted and T cell tropic cytokines like IL-2 and IL-6 (68), or iii) reactivation of latent viruses such as CMV or EBV, which have been shown to be associated with the increased appearance of CD3+CD27-CD28- PB T cells previously (28). This evidence concerns the gene CD28 and diffuse large B-cell lymphoma.