PMID- 12973034
OWN - NLM
STAT- MEDLINE
DCOM- 20040409
LR  - 20191107
IS  - 1524-9557 (Print)
IS  - 1524-9557 (Linking)
VI  - 26
IP  - 5
DP  - 2003 Sep-Oct
TI  - Potent maturation of monocyte-derived dendritic cells after CD40L lentiviral gene 
      delivery.
PG  - 451-60
AB  - Dendritic cells (DCs) are being evaluated in immunization protocols to enhance 
      immunity against infectious diseases and cancer. Interaction of T-helper cells 
      expressing CD40 ligand (CD40L) with its cognate CD40 receptor on DCs leads to a 
      mature DC phenotype, characterized by increased capacity of antigen presentation 
      to cytotoxic T cells. The authors examined the ability of third-generation 
      self-inactivating lentiviral vectors expressing CD40L to induce autonomous 
      maturation of ex vivo expanded human monocyte-derived dendritic cells. 
      Transduction with lentiviral vectors achieved a highly efficient gene transfer of 
      CD40L to DCs, which correlated with phenotypic maturation as shown by the 
      expression of immunologic relevant markers (CD83, CD80, MHCI) and secretion of 
      IL-12, whereas DC phenotype was not affected by a control vector expressing only 
      the green fluorescent protein marker. Addition of recombinant IFN-gamma to DCs at 
      the time of CD40L transduction further enhanced IL-12 production, and when 
      co-cultured with allogeneic and autologous CD8+ and CD4+ T cells, a potent 
      activation was observed. Autologous responses against an HLA-A2-restricted 
      influenza peptide (Flu-M1) and a tumor-associated antigenic peptide (gp100 210M) 
      were significantly enhanced when CD40L transduced DCs were used as 
      antigen-presenting cells for in vitro stimulation of CD8+ cytotoxic T 
      lymphocytes. These results demonstrate that endogenous expression of CD40L by 
      lentivirally transduced DCs induced their autonomous maturation to a phenotype 
      comparable to that induced by optimal concentrations of soluble CD40L, providing 
      a novel tool for genetic manipulation of DCs.
FAU - Koya, Richard C
AU  - Koya RC
AD  - Institute for Genetic Medicine, Keck School of Medicine, University of Southern 
      California, Los Angeles, California, USA.
FAU - Kasahara, Nori
AU  - Kasahara N
FAU - Favaro, Patricia M B
AU  - Favaro PM
FAU - Lau, Roy
AU  - Lau R
FAU - Ta, Huy Q
AU  - Ta HQ
FAU - Weber, Jeffrey S
AU  - Weber JS
FAU - Stripecke, Renata
AU  - Stripecke R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Recombinant Proteins)
RN  - 147205-72-9 (CD40 Ligand)
RN  - 187348-17-0 (Interleukin-12)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Antibodies, Monoclonal
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD40 Ligand/biosynthesis/*genetics/immunology
MH  - Cell Line
MH  - Coculture Techniques
MH  - Dendritic Cells/cytology/*immunology
MH  - *Gene Transfer Techniques
MH  - *Genetic Vectors
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology
MH  - Humans
MH  - Immunophenotyping
MH  - Interleukin-12/biosynthesis
MH  - Lentivirus/*genetics
MH  - Monocytes
MH  - Recombinant Proteins
MH  - T-Lymphocytes, Cytotoxic/immunology
EDAT- 2003/09/16 05:00
MHDA- 2004/04/10 05:00
CRDT- 2003/09/16 05:00
PHST- 2003/09/16 05:00 [pubmed]
PHST- 2004/04/10 05:00 [medline]
PHST- 2003/09/16 05:00 [entrez]
AID - 10.1097/00002371-200309000-00008 [doi]
PST - ppublish
SO  - J Immunother. 2003 Sep-Oct;26(5):451-60. doi: 10.1097/00002371-200309000-00008.