• Home
  • Search Results
  • Type 1-programmed dendritic cells drive antigen-specific latency reversal and immune elimination of persistent HIV-1.

Type 1-programmed dendritic cells drive antigen-specific latency reversal and immune elimination of persistent HIV-1.

EBioMedicine (2019-04-07)
Jan Kristoff, Mariana L Palma, Tatiana M Garcia-Bates, Chengli Shen, Nicolas Sluis-Cremer, Phalguni Gupta, Charles R Rinaldo, Robbie B Mailliard
ABSTRACT

Despite the success of antiretroviral therapy (ART), latent HIV-1 continues to persist in a long-lived population of resting memory CD4+ T cells within those who are infected. Finding a safe and effective means to induce latency reversal (LR) during ART to specifically expose this latent HIV-1 cellular reservoir for immune elimination has been a major barrier to a functional cure. In this study, we test the use of antigen-presenting type 1-polarized, monocyte-derived dendritic cells (MDC1) generated from chronic HIV-1-infected individuals on ART as a means to induce HIV-1 latency reversal in autologous CD4+ T cells harboring replication-competent provirus. We use the same MDC1 for ex-vivo generation of autologous HIV-1 antigen-specific CD8+ cytotoxic T cells (CTL) and test their effector responses against the MDC1-exposed HIV-1- infected CD4+ T cell targets. MDC1 presentation of either HIV-1 or cytomegalovirus (CMV) antigens to CD4+ T cells facilitated HIV-1 LR. This antigen-driven MDC1-mediated LR was sharply diminished with blockade of the CD40L/CD40 'helper' signaling pathway. Importantly, these antigen-presenting MDC1 also activated the expansion of CTL capable of killing the exposed HIV-1-infected targets. Inclusion of virus-associated MHC class II 'helper' antigens in MDC1-based HIV-1 immunotherapies could serve both as a targeted means to safely unmask antigen-specific CD4+ T cells harboring HIV-1, and to support CTL responses that can effectively target the MDC1-exposed HIV-1 cellular reservoir as a functional cure strategy. FUND: This study was supported by the NIH-NAID grants R21-AI131763, U01-AI35041, UM1-AI126603, and T32-AI065380.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Polyinosinic–polycytidylic acid potassium salt, with buffer salts, TLR ligand tested
Sigma-Aldrich
Prostaglandin E2, γ-irradiated, powder, BioXtra, suitable for cell culture
Sigma-Aldrich
5-Norbornene-2-endo,3-exo-dicarboxylic acid, 97%
Sigma-Aldrich
Boc-Asn-OH, ≥98.5% (T)
Sigma-Aldrich
HIV-1 gag, ≥95% (SDS-PAGE), recombinant, expressed in E. coli, Galactosidase-tagged