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-reactive cytotoxic lymphocytes, ranging from 1/190 to 1/12205 were detectable in EBV(-) and EBV(+) donors, as well as in the cord blood of 15 out of 20 neonates, Surface phenotype analysis, depletion experiments with MoAbs specific for T and natural killer (NK) lymphocyte subsets, and T lymphocyte cloning procedures strongly indicate virus-specific cytotoxic T lymphocytes (CTL) as the major population responsible for the lysis of autologous EBV-LCL in EBV(+) donors. Conversely, a high frequency of NK cells seems to be involved in the killing activity observed 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 responsible for IL-2 production in EBV(+) individuals, while CD4(+) T cells 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 immunity, directed against autologous EBV-infefted cells, mediated by both NK cells and CD4(+) T lymphocytes. This characteristic may be relevant for protection against viral infections in both neonates and patients given cord blood transplantation (CBT).