HOMOLOGOUS T-CELL AND B-CELL IMMORTALIZED IN-VITRO BY THE EPSTEIN-BARR-VIRUS EXHIBIT DIFFERENTIAL GENETIC AND FUNCTIONAL FEATURES

After in vitro EBV infection of peripheral blood lymphocytes (PBL), we previously obtained IL-2-independent T-cell lines expressing EBNA1 an d LMP1 viral latent genes. One tumorigenic clone, NC5, was further cha racterized for chromosomal abnormalities, rearrangement and expression of oncogenes, and constitutive or induced activation of cellular tran sduction pathways. NC5 as well as TC cells derived from an NC5-induced tumor exhibited the same few chromosomal abnormalities absent in norm al PBL and B-cell lines (LCLs) from the same donor. No rearrangement o r altered expression of C-MYC, BCL-2 and NF-KB2 oncogenes could be det ected. In contrast, we found high levels of BCL-X and thioredoxin (TRX ), as markers of EBV infection or T-cell activation/transformation sta tus. No constitutive activation of NF-kappa B or STAT transcriptional complexes was observed in these cells. For NF-kappa B, this was in app arent contradiction with its reported inducibility mediated by LMP1, t aking into account that NF-kappa B was still inducible by TNF alpha or PMA and ionomycin. Our results highlight independence of EBV protein- mediated transformation towards classical cellular pathways in T-lymph ocytes.