T-Cell Lymphomas Containing Epstein–Barr Viral DNA in Patients with Chronic Epstein–Barr Virus Infections

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Abstract
Fatal T-cell lymphomas developed in three patients with a chronic illness manifested by fever, pneumonia, dysgammaglobulinemia, hematologic abnormalities, and extraordinarily high titers of antibody to the Epstein–Barr virus (EBV) capsid antigen (>10,000) and early antigen (>640) but low titers to the EBV nuclear antigen (≤40). To understand the pathogenesis of these tumors better, we determined the immunophenotype of the tumor cells and analyzed tumor-cell DNA for EBV genomes and for lymphoid-cell gene rearrangements. More than 80 percent of the cells in tumors had an activated helper T-cell phenotype (T4, T11, la positive). The EBV genome was found by in situ hybridization in tumor tissue from each patient. Southern blot assay of DNA digests from one patient showed the same pattern as that of the EBV-infected marmoset line, B95–8. DNA digests from two patients showed a monoclonal proliferation of T cells determined on the basis of uniform T-cell–receptor gene rearrangements and a single band for the joined termini of the EBV genome.