In vivo transduction of thymic dendritic cells with adenovirus and its potential use in acute inflammatory diseases.
Dendritic cells (DC) represent a potential target for gene therapy. In their ability to process antigens and present them to T cells, DC have been allocated a unique role as initiators of the immune response in both the innate and acquired immunity. Recent in vitro studies have showed the feasibility of DC transduction with adenoviral recombinants. In cancer therapy, targeting of DC with adenovirus has been proved to be effective in inhibiting tumour growth, as well as in reducing the number of tumour metastases. The aim of our study is to evaluate the feasibility of in vivo transduction of DC in a murine lymphocyte-rich compartment (thymus) as a potential treatment for acute inflammatory diseases. Nearly 50% of the total thymic DC were transduced with a first-generation adenoviral construct following intrathymic injection, and post-transductional inflammation was neglectable. Transduction of thymic cells with adenoviral recombinants was able to induce the expression of an intracellular protein (beta-galactosidase, green fluorescent protein), as well as the secretion of human interleukin-10, within the local compartment. Furthermore, this induction of the latter significantly decreased thymic apoptosis in the applied model of acute bacterial peritonitis (cecal ligation and puncture).
Oberholzer
C
C
Department of Trauma and Reconstructive Surgery, CHARITE- University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany. oberhal@mail.surgery.ufl.edu
Tschoeke
S K
SK
Bahjat
K
K
LaFace
D
D
Hutchins
B
B
Clare-Salzler
M J
MJ
Moldawer
L L
LL
Oberholzer
A
A
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018805:Sepsis / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D014161:Transduction, Genetic; D019076:Transgenes; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D049452:Green Fluorescent Proteins; D001616:beta-Galactosidase; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases