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. 2016 Jul;22(7):754-61.
doi: 10.1038/nm.4113. Epub 2016 May 30.

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

Riddhima Banga  1 , Francesco Andrea Procopio  1 , Alessandra Noto  1 , Georgios Pollakis  2 , Matthias Cavassini  3 , Khalid Ohmiti  1 , Jean-Marc Corpataux  4 , Laurence de Leval  5 , Giuseppe Pantaleo  1   6 , Matthieu Perreau  1
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PD-1(+) and follicular helper T cells are responsible for persistent HIV-1 transcription in treated aviremic individuals

Riddhima Banga et al. Nat Med. 2016 Jul.

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.

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