Document Detail

Preconditioning therapy with lentiviral vector-programmed dendritic cells accelerates the homeostatic expansion of antigen-reactive human T cells in NOD.Rag1-/-.IL-2rγc-/- mice.
MedLine Citation:
PMID:  21574869     Owner:  NLM     Status:  MEDLINE    
Dendritic cell (DC)-based immunization is a potent strategy to direct prompt and durable immune responses against viral reactivations after transplantations. Here, we show that overnight lentiviral vector (LV) gene transfer into human monocytes co-expressing granulocyte-macrophage colony stimulating factor and interleukin (IL)-4 induced self-differentiated DCs (SMART-DCs) with stable DC immunophenotype over weeks in culture and secreted several inflammatory cytokines. SMART-DCs injected subcutaneously in immunodeficient NOD.Rag1(-/-).IL2rγ(-/-) (NRG) mice 1 day after LV transduction were stable for a month in vivo. "Conventional" DCs (cDCs) and SMART-DCs were compared with regard to their potency to accelerate the expansion, biodistribution, and antigenic stimulation of autologous human T cells. Peripheral blood cells obtained from human cytomegalovirus (hCMV)-reactive donors and full-length hCMV pp65 antigenic protein or peptides were used. DCs loaded with pp65 were administered subcutaneously into NRG mice as a preconditioning treatment a week prior to intravenous infusion with T cells. Optical imaging analyses demonstrated that in mice preconditioned with SMART-DC-pp65, T cells were directly recruited to the immunization site and subsequently spread to the spleen and other organs. A dramatic expansion of both human CD8(+) and CD4(+) T cells could be observed within a few days after infusion, and this was associated with consistent measurable CD8(+) effector memory T-cell responses against different pp65 epitopes. Thus, this mouse model demonstrates the proof-of-principle for SMART-DCs to accelerate expansion of human lymphocytes, resulting in poly-functional and antigen-specific immune responses against hCMV-pp65.
Gustavo Salguero; Bala Sai Sundarasetty; Sylvia Borchers; Dirk Wedekind; Britta Eiz-Vesper; Sarvari Velaga; Adan C Jirmo; Georg Behrens; Gregor Warnecke; Ann-Kathrin Knöfel; Rainer Blasczyk; Eva Mischak-Weissinger; Arnold Ganser; Renata Stripecke
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Publication Detail:
Type:  Comparative Study; Journal Article     Date:  2011-07-27
Journal Detail:
Title:  Human gene therapy     Volume:  22     ISSN:  1557-7422     ISO Abbreviation:  Hum. Gene Ther.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-11-02     Completed Date:  2012-02-21     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  9008950     Medline TA:  Hum Gene Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1209-24     Citation Subset:  IM    
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Carl Neuberg Strasse 1, Hannover, Germany .
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MeSH Terms
CD4-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / immunology*
Cell Differentiation / immunology
Cell Proliferation
Dendritic Cells / immunology*,  metabolism,  transplantation*
Genes, RAG-1 / genetics
Genetic Vectors / administration & dosage,  genetics,  metabolism
Immunologic Memory / immunology
Immunotherapy / methods*
Interleukin Receptor Common gamma Subunit / genetics
Lymphopenia / therapy*
Mice, Inbred NOD
Mice, Knockout
Monocytes / cytology
Opportunistic Infections / prevention & control*,  virology
Phosphoproteins / immunology
Transduction, Genetic
Viral Matrix Proteins / immunology
Reg. No./Substance:
0/Interleukin Receptor Common gamma Subunit; 0/Phosphoproteins; 0/Viral Matrix Proteins; 0/cytomegalovirus matrix protein 65kDa

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