Evidence map›Paper›PMID 24498287›Full record

ArticlePloS one2014

Regulatory T cells expanded from HIV-1-infected individuals maintain phenotype, TCR repertoire and suppressive capacity.

Mathieu Angin, Paul L Klarenbeek, Melanie King, Siddhartha M Sharma, Eshia S Moodley, Ashley Rezai, Alicja Piechocka-Trocha, Ildiko Toth, Andrew T Chan, Philip J Goulder and 3 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.5field-weighted citation impact, top 34% 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

7 citing papers in PubMed, 8 citations in OpenAlex.

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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

13 authors at 4 institutions in 5 countries.

Mathieu AnginRagon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America.
Paul L KlarenbeekDepartment of Clinical Immunology and Rheumatology, Academic Medical Center, Amsterdam, The Netherlands.
Melanie KingRagon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America.
Siddhartha M SharmaRagon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America.
Eshia S MoodleyHIV Pathogenesis Programme, Doris Duke Medical Research Institute and KwaZulu-Natal Research Institute for TB and HIV, University of KwaZulu-Natal, Durban, South Africa.
Ashley RezaiRagon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America.
Alicja Piechocka-TrochaRagon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America.
Ildiko TothRagon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America.
Andrew T ChanMassachusetts General Hospital, Gastrointestinal Unit, Boston, Massachusetts, United States of America.
Philip J GoulderHIV Pathogenesis Programme, Doris Duke Medical Research Institute and KwaZulu-Natal Research Institute for TB and HIV, University of KwaZulu-Natal, Durban, South Africa ; Department of Paediatrics, University of Oxford, Oxford, United Kingdom.
Thumbi Ndung'uRagon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America ; HIV Pathogenesis Programme, Doris Duke Medical Research Institute and KwaZulu-Natal Research Institute for TB and HIV, University of KwaZulu-Natal, Durban, South Africa.
Douglas S KwonRagon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America ; Massachusetts General Hospital, Division of Infectious Diseases, Boston, Massachusetts, United States of America.
Marylyn M AddoRagon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America ; Massachusetts General Hospital, Division of Infectious Diseases, Boston, Massachusetts, United States of America ; Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Ragon Institute of MGH, MIT and Harvard · USMassachusetts General Hospital · USUniversity of KwaZulu-Natal · ZAAcademic Medical Center · NL

Funding

The impact of HIV viral diversity and cellular immunity on HIV pathogenesisP30AI060354 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI ROBERT A. PARKER · 2004 to 2026
$94.4M
Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3M
T cell regulation: CD4+CD25+ FOXP3+ T cells in acute and chronic HIV-1 infectionK08AI074405 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI ADDO, MARYLYN MARTINA · 2007 to 2010
$610k
NIAID NIH HHS 5P30AI060354-09NIAID NIH HHS AI074405-03S1NIAID NIH HHS K08 AI074405NIAID NIH HHS P30 AI060354NIDDK NIH HHS P30 DK043351NIDDK NIH HHS P30DK043351
6 · The paper itself

Abstract

While modulation of regulatory T cell (Treg) function and adoptive Treg transfer are being explored as therapeutic modalities in the context of autoimmune diseases, transplantation and cancer, their role in HIV-1 pathogenesis remains less well defined. Controversy persists regarding their beneficial or detrimental effects in HIV-1 disease, which warrants further detailed exploration. Our objectives were to investigate if functional CD4(+) Tregs can be isolated and expanded from HIV-1-infected individuals for experimental or potential future therapeutic use and to determine phenotype and suppressive capacity of expanded Tregs from HIV-1 positive blood and tissue. Tregs and conventional T cell controls were isolated from blood and gut-associated lymphoid tissue of individuals with HIV-1 infection and healthy donors using flow-based cell-sorting. The phenotype of expanded Tregs was assessed by flow-cytometry and quantitative PCR. T-cell receptor ß-chain (TCR-β) repertoire diversity was investigated by deep sequencing. Flow-based T-cell proliferation and chromium release cytotoxicity assays were used to determine Treg suppressive function. Tregs from HIV-1 positive individuals, including infants, were successfully expanded from PBMC and GALT. Expanded Tregs expressed high levels of FOXP3, CTLA4, CD39 and HELIOS and exhibited a highly demethylated TSDR (Treg-specific demethylated region), characteristic of Treg lineage. The TCRß repertoire was maintained following Treg expansion and expanded Tregs remained highly suppressive in vitro. Our data demonstrate that Tregs can be expanded from blood and tissue compartments of HIV-1+ donors with preservation of Treg phenotype, function and TCR repertoire. These results are highly relevant for the investigation of potential future therapeutic use, as currently investigated for other disease states and hold great promise for detailed studies on the role of Tregs in HIV-1 infection.

Indexed as

Cell ProliferationAdultCells, CulturedCytotoxicity, ImmunologicDNA MethylationFemaleFlow CytometryForkhead Transcription FactorsGastrointestinal TractGene ExpressionHigh-Throughput Nucleotide SequencingHIV-1HIV InfectionsHost-Pathogen InteractionsHumansImmunophenotypingForkhead Transcription FactorsFOXP3 protein, humanReceptors, Antigen, T-Cell

Identifiers

PMID24498287
PMCPMC3911933
OpenAlexW2099945919

What OpenQuestion holds

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Registered trials

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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.