BIOMAT Database Logo BIOMAT Database Logo

Adeno-associated virus type 2 (AAV2) capsid-specific cytotoxic T lymphocytes eliminate only vector-transduced cells coexpressing the AAV2 capsid in vivo. 2007

Chengwen Li, and Matthew Hirsch, and Aravind Asokan, and Brian Zeithaml, and Hong Ma, and Tal Kafri, and R Jude Samulski
Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

A recent clinical trial has suggested that recombinant adeno-associated virus (rAAV) vector transduction in humans induces a cytotoxic T-lymphocyte (CTL) response against the AAV2 capsid. To directly address the ability of AAV capsid-specific CTLs to eliminate rAAV-transduced cells in vitro and in vivo in mice, we first demonstrated that AAV2 capsid-specific CTLs could be induced by dendritic cells with endogenous AAV2 capsid expression or pulsed with AAV2 vectors. These CTLs were able to kill a cell line stable for capsid expression in vitro and also in a mouse tumor xenograft model in vivo. Parent colon carcinoma (CT26) cells transduced with a large amount of AAV2 vectors in vitro were also destroyed by these CTLs. To determine the effect of CTLs on the elimination of target cells transduced by AAV2 vectors in vivo, we carried out adoptive transfer experiments. CTLs eliminated liver cells with endogenous AAV2 capsid expression but not liver cells transduced by AAV2 vectors, regardless of the reporter genes. Similar results were obtained for rAAV2 transduction in muscle. Our data strongly suggest that AAV vector-transduced cells are rarely eliminated by AAV2 capsid-specific CTLs in vivo, even though the AAV capsid can induce a CTL response. In conclusion, AAV capsid-specific CTLs do not appear to play a role in elimination of rAAV-transduced cells in a mouse model. In addition, our data suggest that the mouse model may not mimic the immune response noted in humans and additional modification to AAV vectors may be required for further study in order to elicit a similar cellular immune response.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D009132 Muscles Contractile tissue that produces movement in animals. Muscle Tissue,Muscle,Muscle Tissues,Tissue, Muscle,Tissues, Muscle
D002213 Capsid The outer protein protective shell of a virus, which protects the viral nucleic acid. Capsids are composed of repeating units (capsomers or capsomeres) of CAPSID PROTEINS which when assembled together form either an icosahedral or helical shape. Procapsid,Prohead,Capsids,Procapsids,Proheads
D005822 Genetic Vectors DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition. Cloning Vectors,Shuttle Vectors,Vectors, Genetic,Cloning Vector,Genetic Vector,Shuttle Vector,Vector, Cloning,Vector, Genetic,Vector, Shuttle,Vectors, Cloning,Vectors, Shuttle
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000229 Dependovirus A genus of the family PARVOVIRIDAE, subfamily PARVOVIRINAE, which are dependent on a coinfection with helper adenoviruses or herpesviruses for their efficient replication. The type species is Adeno-associated virus 2. Adeno-Associated Viruses,Dependoparvovirus,Adeno-Associated Virus,Virus, Adeno-Associated,Viruses, Adeno-Associated,Adeno Associated Virus,Adeno Associated Viruses,Dependoparvoviruses,Dependoviruses,Virus, Adeno Associated,Viruses, Adeno Associated
D013602 T-Lymphocytes, Cytotoxic Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2. Cell-Mediated Lympholytic Cells,Cytotoxic T Cells,Cytotoxic T Lymphocyte,Cytotoxic T-Lymphocytes,TC1 Cell,TC1 Cells,TC2 Cell,TC2 Cells,Cell Mediated Lympholytic Cells,Cell, Cell-Mediated Lympholytic,Cell, TC1,Cell, TC2,Cell-Mediated Lympholytic Cell,Cytotoxic T Cell,Cytotoxic T Lymphocytes,Cytotoxic T-Lymphocyte,Lymphocyte, Cytotoxic T,Lympholytic Cell, Cell-Mediated,Lympholytic Cells, Cell-Mediated,T Cell, Cytotoxic,T Lymphocyte, Cytotoxic,T Lymphocytes, Cytotoxic,T-Lymphocyte, Cytotoxic
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines

Related Publications

Chengwen Li, and Matthew Hirsch, and Aravind Asokan, and Brian Zeithaml, and Hong Ma, and Tal Kafri, and R Jude Samulski
Mutational analysis of the adeno-associated virus type 2 (AAV2) capsid gene and construction of AAV2 vectors with altered tropism.
September 2000, Journal of virology,
Chengwen Li, and Matthew Hirsch, and Aravind Asokan, and Brian Zeithaml, and Hong Ma, and Tal Kafri, and R Jude Samulski
Methylation Status of the Adeno-Associated Virus Type 2 (AAV2).
January 2019, Viruses,
Chengwen Li, and Matthew Hirsch, and Aravind Asokan, and Brian Zeithaml, and Hong Ma, and Tal Kafri, and R Jude Samulski
Feline immunodeficiency virus (FIV)-specific cytotoxic T lymphocytes from chronically infected cats are induced in vitro by retroviral vector-transduced feline T cells expressing the FIV capsid protein.
June 1995, Virology,
Chengwen Li, and Matthew Hirsch, and Aravind Asokan, and Brian Zeithaml, and Hong Ma, and Tal Kafri, and R Jude Samulski
Retroviral vector-transduced cells expressing the core polyprotein induce feline immunodeficiency virus-specific cytotoxic T-lymphocytes from infected cats.
October 1995, Virus research,
Chengwen Li, and Matthew Hirsch, and Aravind Asokan, and Brian Zeithaml, and Hong Ma, and Tal Kafri, and R Jude Samulski
Engineered AAV vector minimizes in vivo targeting of transduced hepatocytes by capsid-specific CD8+ T cells.
March 2013, Blood,
Chengwen Li, and Matthew Hirsch, and Aravind Asokan, and Brian Zeithaml, and Hong Ma, and Tal Kafri, and R Jude Samulski
Optimization of the capsid of recombinant adeno-associated virus 2 (AAV2) vectors: the final threshold?
January 2013, PloS one,
Chengwen Li, and Matthew Hirsch, and Aravind Asokan, and Brian Zeithaml, and Hong Ma, and Tal Kafri, and R Jude Samulski
Insertional mutagenesis of the adeno-associated virus type 2 (AAV2) capsid gene and generation of AAV2 vectors targeted to alternative cell-surface receptors.
September 2001, Human gene therapy,
Chengwen Li, and Matthew Hirsch, and Aravind Asokan, and Brian Zeithaml, and Hong Ma, and Tal Kafri, and R Jude Samulski
Adeno-associated virus vectors serotype 2 induce prolonged proliferation of capsid-specific CD8+ T cells in mice.
March 2011, Molecular therapy : the journal of the American Society of Gene Therapy,
Chengwen Li, and Matthew Hirsch, and Aravind Asokan, and Brian Zeithaml, and Hong Ma, and Tal Kafri, and R Jude Samulski
Effects of immunosuppression on circulating adeno-associated virus capsid-specific T cells in humans.
April 2013, Human gene therapy,
Chengwen Li, and Matthew Hirsch, and Aravind Asokan, and Brian Zeithaml, and Hong Ma, and Tal Kafri, and R Jude Samulski
Pre-existing AAV capsid-specific CD8+ T cells are unable to eliminate AAV-transduced hepatocytes.
April 2007, Molecular therapy : the journal of the American Society of Gene Therapy,
Copied contents to your clipboard!