Uptake of antigens from modified vaccinia Ankara virus-infected leukocytes enhances the immunostimulatory capacity of dendritic cells.
Cytotherapy
; 13(6): 739-52, 2011 Jul.
Article
en En
| MEDLINE
| ID: mdl-21250864
ABSTRACT
BACKGROUND AIMS:
Modified vaccinia Ankara (MVA) is a promising vaccine vector for infectious diseases and malignancies. It is fundamental to ascertain its tropism in human leukocyte populations and immunostimulatory mechanisms for application in immunotherapy.METHODS:
Human peripheral blood mononuclear cells (PBMC) and leukocyte subpopulations [monocyte-derived dendritic cells (DC), monocytes and B cells] were infected with MVA in order to evaluate their infection rate, changes in surface markers, cytokine expression and apoptosis.RESULTS:
Monocytes, DC and B cells were most susceptible to MVA infection, followed by natural killer (NK) cells. Monocytes were activated strongly, with upregulation of co-stimulatory molecules, major histocompatibility complex (MHC) molecules and chemokine (C-C motif) receptor (CCR7), while immature DC showed partial activation and B cells were inhibited. Furthermore, expression of chemokine (C-X-C motif) ligand (CXCL10), tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-12p70 was enhanced but IL-1ß and IL-10 were stable or even downregulated. MVA induced a high apoptosis rate of antigen-presenting cells (APC). Nevertheless, incubation of MVA-infected leukocytes with uninfected immature DC (iDC) led to complete maturation of the DC. Subsequently, the matured DC were able to stimulate cytomegalovirus (CMV)-immediate early protein (IE1)-specific T cells.CONCLUSIONS:
MVA induces a T-helper (Th)-1-polarizing cytokine expression in APC. Furthermore, incubation of MVA-infected leukocytes with uninfected iDC leads to complete maturation of the DC and may be the basis for cross-presentation of MVA-encoded antigens. Thus this approach seems to be an ideal model for further studies with MVA-encoded viral antigens regarding immunotherapy and vaccination strategies.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Virus Vaccinia
/
Células Dendríticas
/
Leucocitos Mononucleares
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Cytotherapy
Asunto de la revista:
TERAPEUTICA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Alemania