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

Clin Dev Immunol. 2012:2012:184979. doi: 10.1155/2012/184979. Epub 2012 Jul 12.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation
  • CD8-Positive T-Lymphocytes / immunology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Electroporation
  • Gene Transfer Techniques
  • HIV Infections / immunology*
  • HIV Infections / metabolism
  • HIV Infections / therapy
  • HIV-1* / immunology
  • Humans
  • Imidazoles / pharmacology
  • Interferon-gamma / pharmacology
  • Interleukin-12 / genetics
  • Interleukin-12 / metabolism*
  • Lymphocyte Activation
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • gag Gene Products, Human Immunodeficiency Virus / genetics
  • gag Gene Products, Human Immunodeficiency Virus / immunology*

Substances

  • Imidazoles
  • RNA, Messenger
  • gag Gene Products, Human Immunodeficiency Virus
  • Interleukin-12
  • Interferon-gamma
  • resiquimod