Interleukin-12p70 Expression by Dendritic Cells of HIV-1-Infected Patients Fails to Stimulategag-Specific Immune Responses

Abstract

<jats:p>A variety of immune-based therapies has been developed in order to boost or induce protective CD8<jats:sup>+</jats:sup>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<jats:italic>gag</jats:italic>mRNA enhances their capacity to induce HIV<jats:italic>gag</jats:italic>-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)-<jats:italic>γ</jats:italic>. Our results confirm the ability of HxB2<jats:italic>gag</jats:italic>-expressing DCs to expand functional HIV-specific CD8<jats:sup>+</jats:sup>T cells. However, although most of the patients had detectable<jats:italic>gag</jats:italic>-specific CD8<jats:sup>+</jats:sup>T cell responses, no significant differences in the level of expansion of functional CD8<jats:sup>+</jats:sup>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.</jats:p>

Engineering of regulatory T cells by means of mRNA electroporation in a GMP-compliant manner

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