PD-1(+) and follicular helper T cells are responsible for persistent HIV-1 transcription in treated aviremic individuals.
Details
Serval ID
serval:BIB_FCD5348987A9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
PD-1(+) and follicular helper T cells are responsible for persistent HIV-1 transcription in treated aviremic individuals.
Journal
Nature medicine
ISSN
1546-170X (Electronic)
ISSN-L
1078-8956
Publication state
Published
Issued date
07/2016
Peer-reviewed
Oui
Volume
22
Number
7
Pages
754-761
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
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.
Keywords
Adult, Antiretroviral Therapy, Highly Active, CD4-Positive T-Lymphocytes/cytology, CD4-Positive T-Lymphocytes/metabolism, CD4-Positive T-Lymphocytes/virology, Case-Control Studies, Female, HIV Infections/drug therapy, HIV-1/genetics, HIV-1/physiology, Humans, Lymph Nodes/cytology, Lymph Nodes/virology, Male, Middle Aged, Programmed Cell Death 1 Receptor/metabolism, RNA, Viral/metabolism, Receptors, CXCR5/metabolism, T-Lymphocytes, Helper-Inducer/cytology, T-Lymphocytes, Helper-Inducer/metabolism, T-Lymphocytes, Helper-Inducer/virology, Virus Replication
Pubmed
Web of science
Create date
07/06/2016 8:35
Last modification date
20/08/2019 17:27