DENDRITIC CELLS IMPROVE THE GENERATION OF EPSTEIN-BARR VIRUS-SPECIFICCYTOTOXIC T-LYMPHOCYTES FOR THE TREATMENT OF POSTTRANSPLANTATION LYMPHOMA

Background. The use of immunosuppressive therapies after solid organ t ransplantation has been shown to increase a patient's risk for Epstein -Barr virus (EBV)-associated lymphoma. A potential therapy for this di sorder is the adoptive transfer of EBV-specific cytotoxic T lymphocyte s (CTLs). We proposed that dendritic cells (DCs) could be loaded with EBV antigens and be used to improve the in vitro generation of EBV-spe cific CTLs. Methods. Autologous EBV-transformed B-lymphoblastoid cell lines (BLCLs) were generated from normal donors, and CTLs were initiat ed by culturing peripheral blood mo mononuclear cells with DCs alone, disrupted BLCLs alone intact, irradiated BLCLs alone, and DCs loaded w ith disrupted BLCLs. Lytic activities were determined with a 4-hour ch romium-release assay against autologous BLCLs, and statistical calcula tions were performed by a Student t test assuming equal variance. Resu lts, The lytic activity of CTLs generated with DCs loaded with disrupt ed BLCLs reached 78% and was statistically significant (P < .01) at al l effector/target ratios compared with CTLs generated with DCs alone, disrupted BLCLs alone, or intact BLCLs alone. Total numbers of CTLs we re also greater than those of control groups for DCs loaded with disru pted BLCLs. Conclusions. DCs improved the in vitro generation of EBV-s pecific CTLs as evidenced by this group's significantly increased lyti c activity over that of the control group. The improved lytic activity of DC-generated EBV-CTLs suggests that adoptive transfer of these cel ls could lend to a more effective immunotherapeutic response against p osttransplantation EBV-associated lymphoma.