Epstein-barr-virus hypersensitivity of lymphocytes from patients with ataxia-telangiectasia

Ataxia telangiectasia (AT), an autosomal recessive disorder with a high incidence of lymphoreticular malignancies including Epstein-Barr virus (EBV)-induced lymphoproliferative disorders (LPD), was investigated to assess the susceptibility to EBV infection and oncogenesis. When the patients' lymphocytes were infected with B95-8 EBV, there was a tendency toward an enhanced growth in semisolid agar, as compared with the healthy donor counterparts. Among the preparations tested, from 14 patients, 2 cell lines showed extremely high colony forming efficiency. The lymphocytes from patients with AT did not contain a large number of EBV target cells, as determined by the maximum frequency of EBV-determined nuclear antigen (EBNA) induction prior to cellular DNA synthesis. Fourteen different lymphoblastoid cell lines derived from the 14 patients with AT were then examined for their EBV inducibility and superinfectibility. By treatment with 12-O-tetradecanoyl-phorbol-13-acetate TPA) and culturing at a lower temperature of 33-degrees-C, early antigen (EA) induction occurred approximately 6-fold and 5-fold higher, respectively, as compared with the lymphoblastoid cell lines derived from healthy controls. Viral capsid antigen (VCA) was also induced significantly by TPA or culturing at lower temperature in the lines from patients with AT, but only slightly in the control counterparts. When the lymphoblastoid cells from patients with AT were exposed to P3HR-1 EBV, EA and VCA syntheses were approximately 6- and 12-fold higher, respectively, than those in the cells derived from the healthy controls. This evidence suggested B lymphocytes of patients with AT were highly susceptible to EBV infection and possibly linked to the development of EBV-induced LPD.