High and inducible expression of human immunodeficiency virus type 1 (HIV-1) Nef by adenovirus vector does not disturb potent antigen presentation by monocyte-derived dendritic cells.
Numerous studies indicated that Nef is a pleiotropic factor. Although it has been shown that Nef impairs the antigen-presenting activity of dendritic cells, more recent studies have shown no such impairment. This issue is critical for designing a vaccine expressing Nef. To refine our knowledge regarding the effect of Nef on dendritic cells, we developed constitutive and inducible adenovirus vector systems that express high levels of Nef in monocyte-derived dendritic cells (MDDCs). We showed here that Nef expression clearly downregulated CD4 expression of MDDCs but had little or no effect on other surface molecules, including MHC class I. Nef also did not affect the functional maturation of MDDCs. Use of the inducible Nef-expression system clearly revealed that adenovirus infection per se modulates cytokine secretion and the expression of apoptosis-related molecules in MDDCs, whereas Nef had no effect on these functions. Moreover, the antigen-presenting activity of MDDCs was not disturbed by the presence of Nef. On the contrary, we found that Nef-expressing MDDCs generated from HIV-1-infected individuals efficiently activated Nef-reactive T cells. Therefore, although adenovirus vector may modulate some aspects of MDDC function, Nef-expressing adenovirus would be served as one of HIV vaccine candidates.
Yamamoto
Takuya
T
Department of Immunology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
Isogai
Maya
M
Otake
Kaori
K
Tsunetsugu-Yokota
Yasuko
Y
D016915:AIDS Vaccines / Q000276:immunology; D000256:Adenoviridae / Q000235:genetics; D017951:Antigen Presentation / Q000276:immunology*; D015704:CD4 Antigens / Q000096:biosynthesis / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation; D015693:Gene Products, nef / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015754:Genes, nef; D005822:Genetic Vectors / Q000235:genetics; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D009000:Monocytes / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D015704:CD4 Antigens; D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1