Functional T-cell responses generated by dendritic cells expressing the early HIV-1 proteins Tat, Rev and Nef.
The limitations of highly active anti-retroviral therapy (HAART) have necessitated the development of alternative therapeutic strategies. One of the approaches that has gained prominence in recent years is therapeutic vaccination. We decided to assess the capacity of mature dendritic cells, derived from blood monocytes of HIV-1 infected patients, to generate functional T-cell responses. For this purpose, we constructed a chimeric mRNA encoding the proteins Tat, Rev and Nef. The TaReNef encoding information was linked to the HLA class II-targeting sequence of DC-LAMP. Broadly directed HIV-specific CD4(+) and CD8(+) cytotoxic T cells exhibiting a poly-functional cytokine secretion pattern were generated by co-culturing with autologous chimeric mRNA electroporated dendritic cells. Thus, administration of ex vivo generated dendritic cells expressing the early proteins Tat, Rev and Nef might offer a promising approach for therapeutic vaccination in HIV-1 infection.
Allard
Sabine D
SD
The Laboratory of Molecular and Cellular Therapy, Department of Physiology and Immunology, Medical School of the Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium. sabine.allard@uzbrussel.be
Pletinckx
Katrien
K
Breckpot
Karine
K
Heirman
Carlo
C
Bonehill
Aude
A
Michiels
Annelies
A
van Baalen
Carel A
CA
Gruters
Rob A
RA
Osterhaus
Albert D M E
AD
Lacor
Patrick
P
Thielemans
Kris
K
Aerts
Joeri L
JL
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D018274:Electroporation; D015658:HIV Infections / Q000276:immunology; D006801:Humans; D051907:Lysosomal Membrane Proteins / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D017422:Sequence Analysis, DNA; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000096:biosynthesis / Q000276:immunology*; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000096:biosynthesis / Q000276:immunology*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000096:biosynthesis / Q000276:immunology*
D016207:Cytokines; D051907:Lysosomal Membrane Proteins; D011993:Recombinant Fusion Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D054321:rev Gene Products, Human Immunodeficiency Virus; C514860:rev protein, Human Immunodeficiency Virus-1; D054322:tat Gene Products, Human Immunodeficiency Virus