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

R Banga, FA Procopio, A Noto, G Pollakis… - Nature medicine, 2016 - nature.com
R Banga, FA Procopio, A Noto, G Pollakis, M Cavassini, K Ohmiti, JM Corpataux, L De Leval…
Nature medicine, 2016nature.com
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 …
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 (CXCR5PD-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.
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