EPSTEIN-BARR-VIRUS HYPERSENSITIVITY OF LYMPHOCYTES FROM PATIENTS WITHATAXIA-TELANGIECTASIA

Ataxia telangiectasia (AT), an autosomal recessive disorder with a hig h incidence of lymphoreticular malignancies including Epstein-Barr vir us (EBV)-induced lymphoproliferative disorders (LPD), was investigated to assess the susceptibility to EBV infection and oncogenesis. When t he patients' lymphocytes were infected with B95-8 EBV, there was a ten dency toward an enhanced growth in semisolid agar, as compared with th e healthy donor counterparts. Among the preparations tested, from 14 p atients, 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-det ermined nuclear antigen (EBNA) induction prior to cellular DNA synthes is. Fourteen different lymphoblastoid cell lines derived from the 14 p atients with AT were then examined for their EBV inducibility and supe rinfectibility. By treatment with 12-O-tetradecanoyl-phorbol-13-acetat e TPA) and culturing at a lower temperature of 33-degrees-C, early ant igen (EA) induction occurred approximately 6-fold and 5-fold higher, r espectively, as compared with the lymphoblastoid cell lines derived fr om healthy controls. Viral capsid antigen (VCA) was also induced signi ficantly by TPA or culturing at lower temperature in the lines from pa tients with AT, but only slightly in the control counterparts. When th e lymphoblastoid cells from patients with AT were exposed to P3HR-1 EB V, EA and VCA syntheses were approximately 6- and 12-fold higher, resp ectively, than those in the cells derived from the healthy controls. T his evidence suggested B lymphocytes of patients with AT were highly s usceptible to EBV infection and possibly linked to the development of EBV-induced LPD.