INTACT ANTIGEN PRESENTATION FOR EPSTEIN-BARR-VIRUS (EBV) SPECIFIC CTLBY A LYMPHOBLASTOID CELL-LINE ESTABLISHED FROM A PATIENT WITH SEVERE CHRONIC ACTIVE EBV INFECTION

Severe chronic active Epstein-Barr virus (EBV) infection is a lymphopr oliferative disease characterized by extremely high antibody titers to EBV, fever, lymphadenopathy, hepatosplenomegaly, and pancytopenia, wi thout any prior immunological abnormality. A spontaneous lymphoblastoi d cell line was established from a 4-year-old boy with severe chronic active EBV infection. Immunofluorescence and Western blotting analyses showed that the cell line was of B cell origin and expressed Epstein- Barr nuclear antigens 1, 2 3a, 3b and 3c, and latent membrane protein 1, which are reported to be targets for EBV-specific cytotoxic T lymph ocytes (CTL). The cytotoxicity of peripheral blood mononuclear cells d erived from the patient and his HLA-identical sister was assayed again st the cell line. The cell line was recognized and killed by anti-EBV CTL derived from the HLA-identical sister, but the patient's periphera l blood mononuclear cells had no cytotoxicity. We conclude that antige n presentation in the EBV-infected cells from the patient is intact an d sufficient for generation of an EBV-specific CTL response. These obs e rvations suggest that severe chronic active EBV infection may not be caused by impaired EBV-antigen presentation of the infected cells but by imp aired cellular immune responses to the virus. Our results also suggest the therapeutic possibility that this disease may be treated by adoptive transfer of EBV-specific CTL or bone marrow transplantatio n from an HLA-matched donor whose immune response to EBV is intact.