CD4(+) Epstein-Barr virus-specific cytotoxic T-lymphocytes from human umbilical cord blood

Cell Immunol. 1999 Aug 1;195(2):81-8. doi: 10.1006/cimm.1999.1514.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antibodies, Monoclonal / immunology
  • Antigens, CD / analysis
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Line, Transformed
  • Clone Cells / immunology
  • Coculture Techniques
  • Cytotoxicity, Immunologic / drug effects
  • Cytotoxicity, Immunologic / immunology*
  • Egtazic Acid / pharmacology
  • Fas Ligand Protein
  • Fetal Blood / cytology
  • Fetal Blood / immunology*
  • Granzymes
  • HLA-DR Antigens / immunology
  • Herpesvirus 4, Human / immunology*
  • Herpesvirus 4, Human / physiology
  • Humans
  • Immunotherapy, Adoptive
  • Infant, Newborn
  • Interleukin-2 / pharmacology
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • FASLG protein, human
  • Fas Ligand Protein
  • HLA-DR Antigens
  • Interleukin-2
  • Membrane Glycoproteins
  • Egtazic Acid
  • GZMB protein, human
  • Granzymes
  • Serine Endopeptidases