Efficient stimulation of HIV-1-specific T cells using dendritic cells electroporated with mRNA encoding autologous HIV-1 Gag and Env proteins

Blood. 2006 Mar 1;107(5):1818-27. doi: 10.1182/blood-2005-01-0339. Epub 2005 Nov 1.


Infection with human immunodeficiency virus type 1 (HIV-1) is characterized by dysfunction of HIV-1-specific T cells. To control the virus, antigen-loaded dendritic cells (DCs) might be useful to boost and broaden HIV-specific T-cell responses. In the present study, monocyte-derived DCs from nontreated HIV-1-seropositive patients were electroporated with codon-optimized ("humanized") mRNA encoding consensus HxB-2 (hHXB-2) Gag protein. These DCs elicited a strong HIV-1 Gag-specific interferon-gamma (IFN-gamma) response by an HLA-A2-restricted CD8+ T-cell line. Moreover, hHXB-2 gag mRNA-electroporated DCs also triggered IFN-gamma secretion by autologous peripheral blood mononuclear cells (PBMCs), CD4+ T cells, and CD8+ T cells from all patients tested. Next, a novel strategy was developed using autologous virus sequences. Significant specific IFN-gamma T-cell responses were induced in all patients tested by DCs electroporated with patients' autologous polymerase chain reaction (PCR)-amplified and in vitro-transcribed proviral and plasma viral mRNA encoding either Gag or Env. The stimulatory effect was seen on PBMCs, CD8+ T cells, and CD4+ T cells, demonstrating both major histocompatibility complex (MHC) class I and MHC class II antigen presentation. Moreover, a significant interleukin-2 (IL-2) T-cell response was induced by DCs electroporated with hHxB-2 or proviral gag mRNA. These findings open a major perspective for the development of patient-specific immunotherapy for HIV-1 disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer / methods
  • Adult
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Line
  • Dendritic Cells / immunology*
  • Dendritic Cells / transplantation
  • Electroporation
  • Female
  • Gene Products, gag / genetics
  • Gene Products, gag / immunology*
  • Glycoproteins / genetics
  • Glycoproteins / immunology*
  • HIV Seropositivity / immunology*
  • HIV Seropositivity / therapy
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • HLA-A2 Antigen / immunology
  • Humans
  • Interferon-gamma / immunology
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Monocytes / immunology
  • RNA, Viral / genetics
  • RNA, Viral / immunology
  • Transplantation, Autologous
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*


  • Gene Products, gag
  • Glycoproteins
  • HLA-A2 Antigen
  • RNA, Viral
  • Viral Envelope Proteins
  • envelope protein, Feline immunodeficiency virus
  • Interferon-gamma