Having demonstrated that B-CLL cells activated by CD154+/ gp350+ exosomes achieve an activated phenotype, we next wanted to assess whether these B-CLL cells became immunogenic to autologous EBV-and CLL-specific T cells. Given the expected low number of these T cells in peripheral blood, we stimulated 1,5610 7 PBMCs from patients with B-CLL three times within 21 days with lethally irradiated autologous PBMCs that were incubated with different exosomes as described above. One typical experiment is shown in Figure 4 : before the first stimulation on day 0, PBMCs of this patient consisted mainly of malignant B cells with only 4% CD3+ T cells. After the third round of stimulation, cultures incubated with gp350+/CD154+ exosomes almost exclusively contained CD4+ and CD8+ T-cells ( Figure 4A ). In total, stimulation with CD154+/gp350+ exosomes yielded approximately 1610 7 vital cells on day 31, meaning that the CD4+ and CD8+ T cell counts had increased about 25-fold and 15-fold, respectively ( Figure 4B) , while the total cell number slightly decreased ( Figure 4C ). In contrast, no viable cells were detectable in those cultures that were treated with CD154-/gp350exosomes derived from non-transfected 293 cells, or that were left untreated. Thus, stimulation of T cells with B-CLL cells loaded with CD154+/gp350+ exosomes is a powe rful option to selectively expand specific T cells from B-CLL patients in vitro.