Evidence map›Paper›PMID 27384654›Full record

ArticleJournal of virology2016

CD25+ FoxP3+ Memory CD4 T Cells Are Frequent Targets of HIV Infection In Vivo.

Mkunde Chachage, Georgios Pollakis, Edmund Osei Kuffour, Kerstin Haase, Asli Bauer, Yuka Nadai, Lilli Podola, Petra Clowes, Matthias Schiemann, Lynette Henkel and 10 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.4field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 12 citations in OpenAlex.

  1. Tenofovir, Interferon Pathways, and Mucosal Immunity: Implications for People Living With HIV.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. HIV Persistence in Adipose Tissue Reservoirs.Current HIV/AIDS reports · 2018
    Review
  7. Article
  8. Article
  9. Article
  10. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 10 institutions in 3 countries.

Mkunde ChachageNIMR Mbeya Medical Research Centre, Mbeya, Tanzania mchachage@nimr-mmrc.org geldmacher@lrz.uni-muenchen.de.
Georgios PollakisInstitute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.
Edmund Osei KuffourDepartment of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Dusseldorf, Germany.
Kerstin HaaseDepartment of Genome Oriented Bioinformatics, Technische Universität München, Freising, Germany.
Asli BauerNIMR Mbeya Medical Research Centre, Mbeya, Tanzania Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), Munich, Germany.
Yuka NadaiDivision of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), Munich, Germany.
Lilli PodolaNIMR Mbeya Medical Research Centre, Mbeya, Tanzania Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), Munich, Germany.
Petra ClowesNIMR Mbeya Medical Research Centre, Mbeya, Tanzania Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), Munich, Germany.
Matthias SchiemannInstitute for Medical Microbiology, Immunology and Hygiene, Helmholtz Center Munich, Technische Universität München, Munich, Germany Clinical Cooperation Groups Antigen-Specific Immunotherapy and Immune-Monitoring, Helmholtz Center Munich, Technische Universität München, Munich, Germany.
Lynette HenkelInstitute for Medical Microbiology, Immunology and Hygiene, Helmholtz Center Munich, Technische Universität München, Munich, Germany.
Dieter HoffmannInstitute of Virology, Helmholtz Center Munich, Technische Universität München, Munich, Germany.
Sarah JosephMRC Clinical Trials Unit at UCL, London, United Kingdom.
Sabin BhujuGenome Analytics, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Leonard MabokoNIMR Mbeya Medical Research Centre, Mbeya, Tanzania.
Fred Stephen SarfoKwame Nkrumah University of Science & Technology, Kumasi, Ghana.
Kirsten EberhardtBernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
Michael HoelscherDivision of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), Munich, Germany German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany.
Torsten FeldtDepartment of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Dusseldorf, Germany.
Elmar SaathoffDivision of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), Munich, Germany German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany.
Christof GeldmacherDivision of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), Munich, Germany German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany mchachage@nimr-mmrc.org geldmacher@lrz.uni-muenchen.de.
Ludwig-Maximilians-Universität München · DETechnical University of Munich · DEBernhard Nocht Institute for Tropical Medicine · DEDüsseldorf University Hospital · DEGerman Center for Infection Research · DEHeinrich Heine University Düsseldorf · DEHelmholtz Centre for Infection Research · DEKwame Nkrumah University of Science and Technology · GHMRC Clinical Trials Unit at UCL · GBUniversity of Liverpool · GB

Funding

Medical Research Council MC_UU_12023/23
6 · The paper itself

Abstract

unlabelledInterleukin 2 (IL-2) signaling through the IL-2 receptor alpha chain (CD25) facilitates HIV replication in vitro and facilitates homeostatic proliferation of CD25(+) FoxP3(+) CD4(+) T cells. CD25(+) FoxP3(+) CD4(+) T cells may therefore constitute a suitable subset for HIV infection and plasma virion production. CD25(+) FoxP3(+) CD4(+) T cell frequencies, absolute numbers, and the expression of CCR5 and cell cycle marker Ki67 were studied in peripheral blood from HIV(+) and HIV(-) study volunteers. Different memory CD4(+) T cell subsets were then sorted for quantification of cell-associated HIV DNA and phylogenetic analyses of the highly variable EnvV1V3 region in comparison to plasma-derived virus sequences. In HIV(+) subjects, 51% (median) of CD25(+) FoxP3(+) CD4(+) T cells expressed the HIV coreceptor CCR5. Very high frequencies of Ki67(+) cells were detected in CD25(+) FoxP3(+) memory CD4(+) T cells (median, 27.6%) in comparison to CD25(-) FoxP3(-) memory CD4(+) T cells (median, 4.1%; P < 0.0001). HIV DNA content was 15-fold higher in CD25(+) FoxP3(+) memory CD4(+) T cells than in CD25(-) FoxP3(-) T cells (P = 0.003). EnvV1V3 sequences derived from CD25(+) FoxP3(+) memory CD4(+) T cells did not preferentially cluster with plasma-derived sequences. Quasi-identical cell-plasma sequence pairs were rare, and their proportion decreased with the estimated HIV infection duration. These data suggest that specific cellular characteristics of CD25(+) FoxP3(+) memory CD4(+) T cells might facilitate efficient HIV infection in vivo and passage of HIV DNA to cell progeny in the absence of active viral replication. The contribution of this cell population to plasma virion production remains unclear. IMPORTANCE: Despite recent advances in the understanding of AIDS virus pathogenesis, which cell subsets support HIV infection and replication in vivo is incompletely understood. In vitro, the IL-2 signaling pathway and IL-2-dependent cell cycle induction are essential for HIV infection of stimulated T cells. CD25(+) FoxP3(+) memory CD4 T cells, often referred to as regulatory CD4 T cells, depend on IL-2 signaling for homeostatic proliferation in vivo Our results show that CD25(+) FoxP3(+) memory CD4(+) T cells often express the HIV coreceptor CCR5, are significantly more proliferative, and contain more HIV DNA than CD25(-) FoxP3(-) memory CD4 T cell subsets. The specific cellular characteristics of CD25(+) FoxP3(+) memory CD4(+) T cells probably facilitate efficient HIV infection in vivo and passage of HIV DNA to cell progeny in the absence of active viral replication. However, the contribution of this cell subset to plasma viremia remains unclear.

Indexed as

CD4-Positive T-LymphocytesDNA, Viralenv Gene Products, Human Immunodeficiency VirusForkhead Transcription FactorsHIVHIV InfectionsHumansInterleukin-2 Receptor alpha SubunitKi-67 AntigenPhylogenyReceptors, CCR5Sequence Analysis, DNAT-Lymphocyte SubsetsCCR5 protein, humanDNA, Viralenv Gene Products, Human Immunodeficiency VirusForkhead Transcription FactorsFOXP3 protein, humanIL2RA protein, humanInterleukin-2 Receptor alpha SubunitKi-67 AntigenReceptors, CCR5

Identifiers

PMID27384654
PMCPMC5044822
OpenAlexW2474490775

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.