Evidence map›Paper›PMID 28225449›Full record

ArticleAIDS (London, England)2017

IFN-α augments natural killer-mediated antibody-dependent cellular cytotoxicity of HIV-1-infected autologous CD4+ T cells regardless of major histocompatibility complex class 1 downregulation.

Costin Tomescu, Pablo Tebas, Luis J Montaner

Open access · hybridAbstract read
In one paragraph

Article in AIDS (London, England), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

21 citing papers in PubMed, 27 citations in OpenAlex.

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  12. Advances and challenges in immunotherapy of small cell lung cancer.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2020
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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

3 authors at 1 institution in 1 country.

Costin TomescuHIV Immunopathogenesis Laboratory, The Wistar Institute
Pablo TebasDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Luis J MontanerHIV Immunopathogenesis Laboratory, The Wistar Institute
The Wistar Institute · US

Funding

Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI ROBERT GROSS · 1999 to 2026
$78.6M
Tumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Luis J Montaner · 1985 to 2026
$75.9M
University of Pennsylvania HIV Clinical Trials UnitUM1AI069534 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Ian Frank, PABLO TEBAS · 2012 to 2026
$33.0M
First-in-human study of two anti-SARS CoV-2 antibodies in health volunteersUM1AI126620 · NIAID · WISTAR INSTITUTE · PI MONTANER, LUIS J, RILEY, JAMES L. · 2016 to 2021
$24.5M
TRAINING IN HIV PATHOGENESIST32AI007632 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Frederic D Bushman, James L. Riley · 2000 to 2026
$10.6M
Towards Eradication: Reducing Proviral HIV DNA with Interferon-α ImmunotherapyU01AI110434 · NIAID · WISTAR INSTITUTE · PI MONTANER, LUIS J · 2014 to 2017
$7.2M
Antiviral activity of Peg-IFN alpha in chronic HIV-1U01AI065279 · NIAID · WISTAR INSTITUTE · PI MONTANER, LUIS J · 2005 to 2009
$2.8M
APCs and Innate Immunity in HIV DiseaseR01AI051225 · NIAID · WISTAR INSTITUTE · PI MONTANER, LUIS J. · 2002 to 2005
$1.6M
ANTI-HIV-1 EFFECTS OF IL-13 ON MACROPHAGES AND T CELLSR01AI047760 · NIAID · WISTAR INSTITUTE · PI MONTANER, LUIS J. · 2000 to 2004
$1.5M
Direct/Indirect NK Activation by HIV-1 Infected CellsF32AI068405 · NIAID · WISTAR INSTITUTE · PI TOMESCU, COSTIN · 2006 to 2007
$62k
NCI NIH HHS P30 CA010815NIAID NIH HHS F32 AI068405NIAID NIH HHS P30 AI045008NIAID NIH HHS R01 AI047760NIAID NIH HHS R01 AI051225NIAID NIH HHS T32 AI007632NIAID NIH HHS U01 AI065279NIAID NIH HHS U01 AI110434NIAID NIH HHS UM1 AI069534NIAID NIH HHS UM1 AI126620
6 · The paper itself

Abstract

designWe have previously shown that IFN-α stimulation augments direct natural killer (NK) cell lysis of autologous CD4 primary T cells infected with certain HIV-1 isolates based upon major histocompatibility complex class 1 (MHC-1) downregulation capacity. Here, we investigated if antibody-dependent cellular cytotoxicity (ADCC) could trigger lysis of HIV-1 isolates that were resistant to direct NK lysis and if IFN-α prestimulation of NK cells could further enhance ADCC.

methodsUsing broadly neutralizing monoclonal antibodies against gp120 (VRC01 or PGV04) or plasma from HIV-1-infected patients (ART-suppressed or elite controller) to trigger ADCC, we measured NK cell chromium release cytotoxicity against HIV-1-infected autologous CD4 primary T cells and NK cell CD107a degranulation against gp120-coated CD4 T cells. Total or NK-depleted peripheral blood mononuclear cells were used as effectors in the presence or absence of IFN-α prestimulation.

resultsPlasma from HIV-1-infected patients and monoclonal antibodies against gp120 could trigger NK-dependent ADCC lysis of viral isolates that were resistant to direct NK cell lysis following IFN-α stimulation. In contrast, viral isolates that exhibited potent MHC-I downregulation capacity could be lysed by NK cells through either IFN-α stimulated direct cytotoxicity or through ADCC. When utilized in combination, IFN-α prestimulation significantly augmented ADCC lysis of HIV-1-infected target cells and increased NK cell CD107a degranulation against gp120-coated ADCC targets (P < 0.05, n = 6).

conclusionHIV-1 isolates with lower MHC-I downregulation capacity are resistant to direct lysis following IFN-α stimulation but retain sensitivity to ADCC. IFN-α prestimulation can significantly increase NK-mediated clearance of HIV-1-infected target cells by both ADCC and/or direct cytotoxicity depending on MHC downregulation status.

Indexed as

Antibody-Dependent Cell CytotoxicityAntibodies, MonoclonalCD4-Positive T-LymphocytesCells, CulturedDown-RegulationHistocompatibility Antigens Class IHIV AntibodiesHIV InfectionsHumansInterferon-alphaKiller Cells, NaturalAntibodies, MonoclonalHistocompatibility Antigens Class IHIV AntibodiesInterferon-alphaantibody-dependent cellular cytotoxicitycytotoxicityHIV/AIDSnatural killer cellsVRC01

Identifiers

PMID28225449
PMCPMC5934752
OpenAlexW2973822473

What OpenQuestion holds

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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.