Interleukin-12p70 expression by dendritic cells of HIV-1-infected patients fails to stimulate gag-specific immune responses

E. Van Gulck, N. Cools, D. Atkinson, L. Bracke, Katleen Vereecken, M. Vekemans, V.F.I. Van Tendeloo, Z.N. Berneman, G. Vanham

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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 na‹ve 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)-?. 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.
Original languageEnglish
JournalClinical and Developmental Immunology
Volume184979
Pages (from-to)1-11
Number of pages11
ISSN1740-2522
DOIs
Publication statusPublished - 2012

Keywords

  • Viral diseases
  • HIV-1
  • AIDS
  • Virus replication
  • Control
  • Therapy
  • Immune response
  • Gag
  • Interleukin-12p70
  • Dendritic cells
  • T cells
  • mRNA
  • CD8-positive-T-lymphocytes

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