PD-1+ and follicular helper T cells are responsible for persistent HIV-1 transcription in treated aviremic individuals

Banga, R, Procopio, FA, Noto, A, Pollakis, G ORCID: 0000-0002-9659-5461, Cavassini, M, Ohmiti, K, Corpataux, JM, De Leval, L, Pantaleo, G and Perreau, M (2016) PD-1+ and follicular helper T cells are responsible for persistent HIV-1 transcription in treated aviremic individuals. Nature Medicine, 22 (7). pp. 754-761.

Text Manuscript Banga et.al Nat Med.pdf - Author Accepted Manuscript Download (4MB)

Abstract

The mechanisms responsible for the persistence of HIV-1 after many years of suppressive antiretroviral therapy (ART) have been only partially elucidated. Most of the studies investigating HIV-1 persistence have been performed with blood, although it is well known that germinal centers (GCs) within lymph nodes (LNs) serve as primary sites for HIV-1 replication. We sought to identify the memory CD4 T cell populations in blood and LNs that are responsible for the production of replication-competent and infectious HIV-1, as well as for active and persistent virus transcription in ART-treated (for 1.5-14.0 years), aviremic (<50 HIV RNA copies/ml) HIV-infected individuals. We demonstrate that LN CD4 T cells that express programmed cell death 1 (PDCD1; also known as PD-1), which are composed of about 65% T follicular helper cells as defined by the expression of the cell surface receptors CXCR5 and PD-1, are the major source of replication-competent HIV-1 and of infectious virus, as compared to any other (CXCR5 - PD-1- and CXCR5+ PD-1-) blood or LN memory CD4 T cell populations. LN PD-1+ cells accounted for 46% and 96% of the total pools of memory CD4 T cells containing inducible replication-competent or infectious virus, respectively. Notably, higher levels of cell-associated HIV-1 RNA were present in LN PD-1+ cells after long-term (up to 12 years) ART than in other memory CD4 T cell subpopulations. These results indicate that LN PD-1+ cells are the major CD4 T cell compartment in the blood and LNs for the production of replication-competent and infectious HIV-1, and for active and persistent virus transcription in long-term-ART-treated aviremic individuals. Thus, these cells may represent a major obstacle to finding a functional cure for HIV-1 infection.

Item Type:	Article
Uncontrolled Keywords:	Immunology, Lymphoid tissues
Depositing User:	Symplectic Admin
Date Deposited:	04 Mar 2019 08:37
Last Modified:	08 Feb 2023 06:26
DOI:	10.1038/nm.4113
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3033647