Document Detail


Rapid selection of antigen-specific T lymphocytes by retroviral transduction.
MedLine Citation:
PMID:  10891438     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Infusions of donor peripheral blood T cells can induce durable remissions of Epstein-Barr virus (EBV) lymphomas complicating marrow grafts, but they contain alloreactive T cells capable of inducing graft-versus-host disease. EBV-specific T-cell lines or clones avoid this problem but require 30 to 40 days of culture to establish. To accelerate the generation of EBV-specific T cells, we tested whether retroviral vectors, which only integrate in dividing cells, could be used to transduce and select antigen-reactive T cells early after sensitization to autologous EBV-transformed B cells. T cells were transduced with a dicistronic retroviral vector, NIT, which encodes low-affinity nerve growth factor receptor as an immunoselectable marker and herpes simplex virus thymidine kinase as a suicide gene, at different time points after sensitization. EBV-specific cytotoxic T lymphocyte precursor (CTLp) frequencies in purified NIT(+) T-cell fractions transduced on day 8 of culture were comparable to those of EBV-specific T-cell lines cultured for 30 days or more. Alloreactive CTLp frequencies were markedly reduced in the NIT(+) fraction relative to the untransduced T-cell population. NIT(+) fractions transduced on day 8 possessed more CD4(+) T cells than the cell lines at day 30 and exhibited the same selective pattern of reactivity against immunodominant antigens presented by specific HLA alleles. In contrast, T cells transduced with NIT 5 days after stimulation with mitogen and interleukin-2 were relatively depleted of T cells specific for autologous EBV-transformed cells. Thus, retroviral vectors may be used for rapid selection of viral antigen-reactive T cells depleted of alloreactive T cells.
Authors:
G Koehne; H F Gallardo; M Sadelain; R J O'Reilly
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Blood     Volume:  96     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2000 Jul 
Date Detail:
Created Date:  2000-08-10     Completed Date:  2000-08-10     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  109-17     Citation Subset:  AIM; IM    
Affiliation:
Bone Marrow Transplant Service, Department of Pediatrics, Memorial Hospital, New York, NY, USA.
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MeSH Terms
Descriptor/Qualifier:
Cytotoxicity, Immunologic
Flow Cytometry / methods
Gene Transfer Techniques*
Genetic Vectors
HLA Antigens / immunology
Herpesvirus 4, Human / genetics*
Humans
Lymphocyte Activation
Retroviridae / genetics
T-Lymphocytes / classification,  immunology*
T-Lymphocytes, Cytotoxic / immunology*,  virology
Virus Integration
Grant Support
ID/Acronym/Agency:
CA23766/CA/NCI NIH HHS; CA59350/CA/NCI NIH HHS; HL53752/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/HLA Antigens

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