Severe chronic EBV infection associated with specific EBV immunodeficiency and an EBNA+ T-cell lymphoma containing linear, EBV DNA.

A patient with severe chronic Epstein-Barr virus (EBV) infection (CEBVI) of 6 years duration developed an EBV+ T-cell lymphoma. To determine whether the development of the T-cell tumor was linked to EBV, we studied this patient's EBV-specific immune response and her T-cell tumor tissue for evidence of EBV infection. Peripheral blood lymphocytes from this patient were systematically studied for immune function and response to EBV. Tumor tissue was examined for EBV genome and for evidence of EBV replication. This patient failed to develop anti-EBV nuclear antigen (EBNA) antibodies and had decreased mitogen responsiveness. Her T-cells showed a broad suppression of both autologous and allogeneic B-cells, which was coincident with clinical hypoimmunoglobulinemia. A selective cytotoxic T-cell defect toward autologous EBV-infected B lymphoblasts, which could not be corrected by the addition of lymphokine-mediated T-cell help, was also documented. A lymph node biopsy taken 5 years after her clinical presentation revealed lymph node architecture completely effaced by a diffuse CD3+, CD4+, Ia+, CR2+ T-cell lymphoma containing EBNA and linear, replicating EBV DNA. Select CEBVI patients with humoral and combined cellular aberrations in the immune response to EBV may be predisposed to the development of EBV+ T-cell tumors.