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

Abstract:

: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.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Banga R,Rebecchini C,Procopio FA,Noto A,Munoz O,Ioannidou K,Fenwick C,Ohmiti K,Cavassini M,Corpataux JM,de Leval L,Pantaleo G,Perreau M

doi

10.1371/journal.ppat.1007918

subject

Has Abstract

pub_date

2019-07-22 00:00:00

pages

e1007918

issue

7

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-19-00505

journal_volume

15

pub_type

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