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Negative Checkpoint Regulatory Molecule 2B4 (CD244) Upregulation Is Associated with Invariant Natural Killer T Cell Alterations and Human Immunodeficiency Virus Disease Progression
Hannover Medical Sch, Germany.
University of Malaya, Malaysia; University of Malaya, Malaysia; School Basic Appl Science, India.
University of Malaya, Malaysia.
University of Malaya, Malaysia.
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2017 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 8, 338Article in journal (Refereed) Published
Abstract [en]

The CD1d-restricted invariant natural killer T (iNKT) cells are implicated in innate immune responses against human immunodeficiency virus (HIV). However, the determinants of cellular dysfunction across the iNKT cells subsets are seldom defined in HIV disease. Herein, we provide evidence for the involvement of the negative checkpoint regulator (NCR) 2B4 in iNKT cell alteration in a well-defined cohort of HIV-seropositive anti-retroviral therapy (ART) naive, ART-treated, and elite controllers (ECs). We report on exaggerated 2B4 expression on iNKT cells of HIV-infected treatment-naive individuals. In sharp contrast to CD4-iNKT cells, 2B4 expression was significantly higher on CD4+ iNKT cell subset. Notably, an increased level of 2B4 on iNKT cells was strongly correlated with parameters associated with HIV disease progression. Further, iNKT cells from ARTnaive individuals were defective in their ability to produce intracellular IFN-gamma Together, our results suggest that the levels of 2B4 expression and the downstream co-inhibitory signaling events may contribute to impaired iNKT cell responses.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA , 2017. Vol. 8, 338
Keyword [en]
invariant natural killer T cells; 2B4; human immunodeficiency virus; inhibitory; IFN-gamma; CD4
National Category
Immunology
Identifiers
URN: urn:nbn:se:liu:diva-136578DOI: 10.3389/fimmu.2017.00338ISI: 000397451800001PubMedID: 28396665OAI: oai:DiVA.org:liu-136578DiVA: diva2:1090004
Note

Funding Agencies|University of Malaya Research [RG50113HTM]; Health and Translational Medicine Cluster; European Molecular Biology Organization (EMBO) Short-Term Fellowship; Deutsches Zentrum fur Infektions forschung [04.810, 04.811]; High Impact Research Grant of the Ministry of Higher Education (MoHE) Malaysia [HIRGA E000001-20001]

Available from: 2017-04-21 Created: 2017-04-21 Last updated: 2017-05-08

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