CD4(+) Epstein-Barr virus-specific cytotoxic T-lymphocytes from human umbilical cord blood.
Umbilical cord blood (CB) is increasingly used for allogeneic hematopoietic stem cell transplantation. To determine whether viral antigen-specific cytotoxic T-lymphocytes (CTL) could be generated from the predominantly naive T-cell populations in CB, CB-derived mononuclear cells were stimulated with autologous Epstein-Barr virus (EBV) transformed B-lymphoblastoid cell lines over several weeks in the presence of recombinant human interleukin-2 (IL-2). By 28 days of culture, T-lymphocytes from all six CB that had been treated with IL-2 displayed EBV-specific cytotoxicity. These cells were largely CD4(+), with complete inhibition of cytotoxicity by anti-CD3 and variable inhibition by anti-HLA DR monoclonal antibodies. The EBV-specific effectors were cloned by limiting dilution, and most of the CTL clones were CD4(+). The cytotoxicity of the CB-derived CD4(+) CTL clones was inhibited by EGTA but not by anti-Fas ligand mAb, suggesting that this cytotoxicity was mediated by perforin/granzyme B. These data indicate that virus-specific CTL can be cultivated and cloned from CB, a human T-cell source that may not have prior in vivo antigenic exposure or reactivity. This finding may have applications in adoptive immunotherapy to recipients of CB transplants.
Sun
Q
Q
The Bone Marrow Transplantation Program, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Burton
R L
RL
Pollok
K E
KE
Emanuel
D J
DJ
Lucas
K G
KG
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002461:Cell Line, Transformed; D002999:Clone Cells / Q000276:immunology; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology*; D004533:Egtazic Acid / Q000494:pharmacology; D053222:Fas Ligand Protein; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology*; D053804:Granzymes; D006684:HLA-DR Antigens / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology* / Q000502:physiology; D006801:Humans; D016219:Immunotherapy, Adoptive; D007231:Infant, Newborn; D007376:Interleukin-2 / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D006684:HLA-DR Antigens; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D004533:Egtazic Acid; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases