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

Journal article

T-follicular helper (Tfh) cells, co-expressing PD-1 and TIGIT, serve as a major cell reservoir for HIV-1 and are responsible for active and persistent HIV-1 transcription after prolonged antiretroviral therapy (ART). However, the precise mechanisms regulating HIV-1 transcription in lymph nodes (LNs) remain unclear. In the present study, we investigated the potential role of immune checkpoint (IC)/IC-Ligand (IC-L) interactions on HIV-1 transcription in LN-microenvironment. We show that PD-L1 (PD-1-ligand) and CD155 (TIGIT-ligand) are predominantly co-expressed on LN migratory (CD1chighCCR7+CD127+) dendritic cells (DCs), that locate predominantly in extra-follicular areas in ART treated individuals. We demonstrate that TCR-mediated HIV production is suppressed in vitro in the presence of recombinant PD-L1 or CD155 and, more importantly, when LN migratory DCs are co-cultured with PD-1+/Tfh cells. These results indicate that LN migratory DCs expressing IC-Ls may more efficiently restrict HIV-1 transcription in the extra-follicular areas and explain the persistence of HIV transcription in PD-1+/Tfh cells after prolonged ART within germinal centers

Authors: Banga, R; Rebecchini, C; Procopio, FA; Noto, A; Munoz, O

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Public Library of Science
• Journal: PLoS Pathogens
• Volume: 15
• Issue: 7
• Pages: e1007918-e1007918
• Publication date: 2019-07-22
• DOI: 10.1371/journal.ppat.1007918
• EISSN: 1553-7374
• ISSN: 1553-7366
• Language: English
• Keywords: B cell; Transcription (linguistics); Antibody; Transcription factor; Biology; Immunology; Immune system; Chemistry; Genetics; Cancer research; Antigen-presenting cell; T cell; Cell biology; Follicular dendritic cells; TIGIT; Germinal center