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

Gulck, Ellen R.A. Van

doi:10.1182/blood-2005-01-0339

Cited by 58 publications

(49 citation statements)

References 54 publications

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“…Using murine cells, Thiele et al (76) recently suggested that the processing of a model Ag by modified vaccinia virus Ankara-infected DC was, in part, dependent on autophagy. Several reports using mRNA transfection (77,78) or single-cycle infection with VSV-pseudotyped HIV particles (46) also suggested that DC present endogenous Ags to HS CD4 + T cells. Our present study revealed that DC infected with replicationcompetent HIV can process and present newly synthesized/ endogenous Gag and Env Ags to HS CD4 + T cells.…”

Section: Discussionmentioning

confidence: 99%

HIV-Infected Dendritic Cells Present Endogenous MHC Class II–Restricted Antigens to HIV-Specific CD4+ T Cells

Coulon

Richetta

Rouers

et al. 2016

The Journal of Immunology

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It is widely assumed that CD4+ T cells recognize antigenic peptides (epitopes) derived solely from incoming, exogenous, viral particles or proteins. However, alternative sources of MHC class II (MHC-II)–restricted Ags have been described, in particular epitopes derived from newly synthesized proteins (so-called endogenous). In this study, we show that HIV-infected dendritic cells (DC) present MHC-II–restricted endogenous viral Ags to HIV-specific (HS) CD4+ T cells. This endogenous pathway functions independently of the exogenous route for HIV Ag presentation and offers a distinct possibility for the immune system to activate HS CD4+ T cells. We examined the implication of autophagy, which plays a crucial role in endogenous viral Ag presentation and thymic selection of CD4+ T cells, in HIV endogenous presentation. We show that infected DC do not use autophagy to process MHC-II–restricted HIV Ags. This is unlikely to correspond to a viral escape from autophagic degradation, as infecting DC with Nef- or Env-deficient HIV strains did not impact HS T cell activation. However, we demonstrate that, in DC, specific targeting of HIV Ags to autophagosomes using a microtubule-associated protein L chain 3 (LC3) fusion protein effectively enhances and broadens HS CD4+ T cell responses, thus favoring an endogenous MHC-II–restricted presentation. In summary, in DC, multiple endogenous presentation pathways lead to the activation of HS CD4+ T cell responses. These findings will help in designing novel strategies to activate HS CD4+ T cells that are required for CTL activation/maintenance and B cell maturation.

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Section: Discussionmentioning

confidence: 99%

HIV-Infected Dendritic Cells Present Endogenous MHC Class II–Restricted Antigens to HIV-Specific CD4+ T Cells

Coulon

Richetta

Rouers

et al. 2016

The Journal of Immunology

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“…formes provirales et plasmatiques du virus [20]. Cette approche a permis de déclencher des réponses T CD4 et CD8 dirigées contre les différents variants individuels du virus qui se répliquent, mais également contre les formes latentes qui constituent les réservoirs du virus.…”

Section: Synthèse Revuesunclassified

Les cellules dendritiques transfectées avec de l’ARN messager

et al. 2007

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“…DNA transfection of DC has been used successfully in some studies but is limited by poor expression levels and toxicity (2,29,41,45,49), although methods to enhance expression based on DC maturation have been proposed (28). mRNA transfection of DC is being increasingly utilized for cancer immunotherapy and in vitro stimulation of virus-specific T cells, but approaches to deliver mRNA into primary DC cultures have been limited (16,18,25,39,40,43,48,50). Transfection of DC with mRNA offers the potential for highlevel expression of wild-type viral transgenes that have poor expression in mammalian cells when traditional methods of gene delivery are used (8,26).…”

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confidence: 99%

High-Level Antigen Expression and Sustained Antigen Presentation in Dendritic Cells Nucleofected with Wild-Type Viral mRNA but Not DNA

Melhem

Gleason

Liu

et al. 2008

Clin Vaccine Immunol

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Dendritic cells (DC) are potent antigen-presenting cells that hold promise as cell-based therapeutic vaccines for infectious diseases and cancer. Ideally, DC would be engineered to express autologous viral or tumor antigens to ensure the presentation of relevant antigens to host T cells in vivo; however, expression of wild-type viral genes in primary cell lines can be problematic. Nucleofection is an effective means of delivering transgenes to primary cell lines, but its use in transfecting DNA or mRNA into DC has not been widely investigated. We show that nucleofection is a superior means of transfecting human and monkey monocyte-derived DC with DNA and mRNA compared to lipofection and conventional electroporation. However, the delivery of DNA and mRNA had significantly different outcomes in transfected DC. DC nucleofected with DNA encoding green fluorescent protein (GFP) had poor antigen expression and viability and were refractory to maturation with CD40 ligand. In contrast, >90% of DC expressed uniform and high levels of GFP from 3 h to 96 h postnucleofection with mRNA while maintaining a normal maturation response to CD40 ligation. Monkey DC nucleofected with wild-type, non-codon-optimized mRNA encoding simian immunodeficiency virus Gag stimulated robust antigen-specific effector T-cell responses at 24 h and 48 h postnucleofection, reflecting sustained antigen presentation in transfected DC, whereas no detectable T-cell response was noted when DC were nucleofected with DNA encoding the same Gag sequence. These data indicate that mRNA nucleofection may be an optimal means of transfecting DC with autologous tumor or viral antigen for DC-based immunotherapy.

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

Cited by 58 publications

References 54 publications

HIV-Infected Dendritic Cells Present Endogenous MHC Class II–Restricted Antigens to HIV-Specific CD4+ T Cells

HIV-Infected Dendritic Cells Present Endogenous MHC Class II–Restricted Antigens to HIV-Specific CD4+ T Cells

Les cellules dendritiques transfectées avec de l’ARN messager

High-Level Antigen Expression and Sustained Antigen Presentation in Dendritic Cells Nucleofected with Wild-Type Viral mRNA but Not DNA

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