Lymph node migratory dendritic cells modulate HIV-1 transcription through PD-1 engagement

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• T-follicular helper (Tfh) cells are key reservoirs for HIV-1, maintaining viral transcription even during long-term antiretroviral therapy (ART).
• The exact mechanisms controlling HIV-1 transcription within lymph nodes (LNs) are not fully understood.
• Immune checkpoints (IC) and their ligands (IC-L) are implicated in immune regulation.

Purpose of the Study:

• To investigate the role of immune checkpoint/ligand interactions in regulating HIV-1 transcription within the lymph node microenvironment.
• To explore how dendritic cells (DCs) influence HIV-1 transcription in Tfh cells.

Main Methods:

• Characterized co-expression of PD-1 and TIGIT on Tfh cells and their ligands (PD-L1, CD155) on migratory dendritic cells (DCs) in lymph nodes of ART-treated individuals.
• Assessed the impact of recombinant PD-L1 and CD155 on T-cell receptor (TCR)-mediated HIV production in vitro.
• Co-cultured lymph node migratory DCs with PD-1+/Tfh cells to evaluate effects on HIV transcription.

Main Results:

• PD-L1 and CD155 were found to be co-expressed on migratory DCs in extra-follicular areas of lymph nodes from individuals on ART.
• Recombinant PD-L1 and CD155 suppressed TCR-mediated HIV production in vitro.
• Co-culture of migratory DCs with PD-1+/Tfh cells also inhibited HIV production.

Conclusions:

• Lymph node migratory DCs expressing immune checkpoint ligands may limit HIV-1 transcription in extra-follicular regions.
• These interactions could contribute to the persistence of HIV-1 transcription in Tfh cells within germinal centers, even after extended ART.