ArticleJournal of immunology (Baltimore, Md. : 1950)2016
Germinal Center T Follicular Helper Cells Are Highly Permissive to HIV-1 and Alter Their Phenotype during Virus Replication.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 86 citations in OpenAlex.
- Delayed gastrointestinal-associated lymphoid tissue reconstitution in duodenum compared with rectum in HIV-infected patients initiating antiretroviral therapy.AIDS (London, England) · 2019Trial
- Anti-α4β7 therapy targets lymphoid aggregates in the gastrointestinal tract of HIV-1-infected individuals.Science translational medicine · 2018Trial
- Phenotypic analysis of productively SIV-infected cells in blood and lymphoid tissues of rhesus macaques.Cell reports · 2026Article
- Modeling HIV infection, treatment, rebound, and intervention in human immune organoids.bioRxiv : the preprint server for biology · 2026Article
- Lymphoid B cells upregulate HIV-1 ex vivo and are linked to its expression in vivo.PLoS pathogens · 2025Article
- Early treatment and PD1 inhibition enhance HIV-specific functionality of follicular CD8+ T cells.JCI insight · 2025Article
- Immune Alterations and Viral Reservoir Atlas in SIV-Infected Chinese Rhesus Macaques.Infectious disease reports · 2025Review
- Article
- Hypermethylation at the CXCR5 gene locus limits trafficking potential of CD8+ T cells into B-cell follicles during HIV-1 infection.Blood advances · 2022Article
- Current Advances in Follicular Regulatory T-Cell Biology.Critical reviews in immunology · 2022Review
- Follicular regulatory T cells eliminate HIV-1-infected follicular helper T cells in an IL-2 concentration dependent manner.Frontiers in immunology · 2022Article
- T-Follicular-Like CD8Frontiers in immunology · 2022Article
- Providing a Helping Hand: Metabolic Regulation of T Follicular Helper Cells and Their Association With Disease.Frontiers in immunology · 2022Review
- Functional differentiation and regulation of follicular T helper cells in inflammation and autoimmunity.Immunology · 2021Review
- Jigsaw falling into place: A review and perspective of lymphoid tissue CD8+ T cells and control of HIV.Molecular immunology · 2020Review
- What Can Gamma Delta T Cells Contribute to an HIV Cure?Frontiers in cellular and infection microbiology · 2020Review
- Immortalizing Mesenchymal Stromal Cells from Aged Donors While Keeping Their Essential Features.Stem cells international · 2020Article
- Follicular Helper T Cells Are Major Human Immunodeficiency Virus-2 Reservoirs and Support Productive Infection.The Journal of infectious diseases · 2020Article
- Review
- Strong TScience translational medicine · 2019Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
HIV-1 replication is concentrated within CD4(+) T cells in B cell follicles of secondary lymphoid tissues during asymptomatic disease. Limited data suggest that a subset of T follicular helper cells (TFH) within germinal centers (GC) is highly permissive to HIV-1. Whether GC TFH are the major HIV-1 virus-producing cells in vivo has not been established. In this study, we investigated TFH permissivity to HIV-1 ex vivo by spinoculating and culturing tonsil cells with HIV-1 GFP reporter viruses. Using flow cytometry, higher percentages of GC TFH (CXCR5(high)PD-1(high)) and CXCR5(+)programmed cell death-1 (PD-1)(low) cells were GFP(+) than non-GC TFH (CXCR5(+)PD-1(intermediate)) or extrafollicular (EF) (CXCR5(-)) cells. When sorted prior to spinoculation, however, GC TFH were substantially more permissive than CXCR5(+)PD-1(low) or EF cells, suggesting that many GC TFH transition to a CXCR5(+)PD-1(low) phenotype during productive infection. In situ hybridization on inguinal lymph node sections from untreated HIV-1-infected individuals without AIDS revealed higher frequencies of HIV-1 RNA(+) cells in GC than non-GC regions of follicle or EF regions. Superinfection of HIV-1-infected individuals' lymph node cells with GFP reporter virus confirmed the permissivity of follicular cells ex vivo. Lymph node immunostaining revealed 96% of CXCR5(+)CD4(+) cells were located in follicles. Within sorted lymph node cells from four HIV-infected individuals, CXCR5(+) subsets harbored 11-66-fold more HIV-1 RNA than CXCR5(-) subsets, as determined by RT PCR. Thus, GC TFH are highly permissive to HIV-1, but downregulate PD-1 and, to a lesser extent, CXCR5 during HIV-1 replication. These data further implicate GC TFH as the major HIV-1-producing cells in chronic asymptomatic HIV-1 infection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.