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 1/12,205 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 1/5072-1/57,819) and in the EBV- adult (1/17,148). 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-infected 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).
Moretta
A
A
Department of Paediatrics, University of Paiva, IRCCS Policlinico San Matteo, Italy.
Comoli
P
P
Montagna
D
D
Gasparoni
A
A
Percivalle
E
E
Carena
I
I
Revello
M G
MG
Gerna
G
G
Mingrat
G
G
Locatelli
F
F
Rondini
G
G
Maccario
R
R
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D019002:CD56 Antigen / Q000032:analysis; D002460:Cell Line / Q000821:virology; D005312:Fetal Blood / Q000166:cytology*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D007231:Infant, Newborn; D007376:Interleukin-2 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic
D019002:CD56 Antigen; D007376:Interleukin-2