HIGH-FREQUENCY OF EPSTEIN-BARR-VIRUS (EBV) LYMPHOBLASTOID CELL LINE-REACTIVE LYMPHOCYTES IN CORD-BLOOD - EVALUATION OF CYTOLYTIC ACTIVITY AND IL-2 PRODUCTION

We investigated natural immunity towards autologous EBV lymphoblastoid cell lines (EBV-LCL) in the cord blood. Cord blood lymphocytes (CBL) from 20 healthy neonates were examined together with three EBV(+) and one EBV(-) adult donors. We found that high frequencies of EBV-LCL-rea ctive cytotoxic lymphocytes, ranging from 1/190 to 1/12205 were detect able in EBV(-) and EBV(+) donors, as well as in the cord blood of 15 o ut of 20 neonates, Surface phenotype analysis, depletion experiments w ith MoAbs specific for T and natural killer (NK) lymphocyte subsets, a nd T lymphocyte cloning procedures strongly indicate virus-specific cy totoxic T lymphocytes (CTL) as the major population responsible for th e lysis of autologous EBV-LCL in EBV(+) donors. Conversely, a high fre quency of NK cells seems to be involved in the killing activity observ ed in neonates and in the EBV(-) donor. Frequencies of EBV-LCL-induced IL-2-producing lymphocytes were high in EBV(+) donors (range 1/2247-1 /6633) and heterogeneous, but consistent, in cord blood (range 1/5072- 1/57819) and in the EBV(-) adult (1/17148). CD8(+) lymphocytes were re sponsible for IL-2 production in EBV(+) individuals, while CD4(+) T ce lls were charged with this role in cord blood and in the EBV(-) donor, These data demonstrate that CBL are able to develop a strong innate i mmunity, directed against autologous EBV-infefted cells, mediated by b oth NK cells and CD4(+) T lymphocytes. This characteristic may be rele vant for protection against viral infections in both neonates and pati ents given cord blood transplantation (CBT).