title: Interleukin-12p70 expression by dendritic cells of HIV-1-infected patients fails to stimulate gag-specific immune responses.
abstract: A variety of immune-based therapies has been developed in order to boost or induce protective CD8(+) T cell responses in order to control HIV replication. Since dendritic cells (DCs) are professional antigen-presenting cells (APCs) with the unique capability to stimulate naïve T cells into effector T cells, their use for the induction of HIV-specific immune responses has been studied intensively. In the present study we investigated whether modulation of the activation state of DCs electroporated with consensus codon-optimized HxB2 gag mRNA enhances their capacity to induce HIV gag-specific T cell responses. To this end, mature DCs were (i) co-electroporated with mRNA encoding interleukin (IL)-12p70 mRNA, or (ii) activated with a cytokine cocktail consisting of R848 and interferon (IFN)-γ. Our results confirm the ability of HxB2 gag-expressing DCs to expand functional HIV-specific CD8(+) T cells. However, although most of the patients had detectable gag-specific CD8(+) T cell responses, no significant differences in the level of expansion of functional CD8(+) T cells could be demonstrated when comparing conventional or immune-modulated DCs expressing IL-12p70. This result which goes against expectation may lead to a re-evaluation of the need for IL-12 expression by DCs in order to improve T-cell responses in HIV-1-infected individuals.
authors: Virology Unit, Department of Microbiology, Institute of Tropical Medicine (ITMA), 2000 Antwerp, Belgium.
authors: Ellen
authors: E
authors: Van Gulck
authors: Nathalie
authors: N
authors: Cools
authors: Derek
authors: D
authors: Atkinson
authors: Lotte
authors: L
authors: Bracke
authors: Katleen
authors: K
authors: Vereecken
authors: Marc
authors: M
authors: Vekemans
authors: Viggo F I
authors: VF
authors: Van Tendeloo
authors: Zwi N
authors: ZN
authors: Berneman
authors: Guido
authors: G
authors: Vanham
mesh_terms: D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D018274:Electroporation; D018014:Gene Transfer Techniques; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D007093:Imidazoles; D012333:RNA, Messenger; D054301:gag Gene Products, Human Immunodeficiency Virus; D018664:Interleukin-12; D007371:Interferon-gamma; C402365:resiquimod