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Brief Report: Diminished Coinhibitory Molecule 2B4 Expression Is Associated With Preserved iNKT Cell Phenotype in HIV Long-Term Nonprogressors
Univ Malaya, Malaysia; Univ Sharjah, U Arab Emirates.
Hannover Med Sch, Germany; Hamad Med Corp, Qatar; Hamad Med Corp, Qatar.
Univ Malaya, Malaysia; Cent Univ Tamil Nadu CUTN, India.
Xiamen Univ Malaysia, Malaysia.
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2020 (English)In: Journal of Acquired Immune Deficiency Syndromes, ISSN 1525-4135, E-ISSN 1944-7884, Vol. 85, no 1, p. 73-78Article in journal (Refereed) Published
Abstract [en]

Background: We have previously shown an association of elevated coinhibitory molecule 2B4 expression with iNKT cells alterations in HIV disease. Herein, we show a comparative analysis of 2B4 expression on iNKT cells of HIV long-term nonprogressors (LTNPs) and progressors. Methods: Antiretroviral therapy-naive HIV-seropositive individuals (progressors, n = 16) and LTNPs (n = 10) were recruited for this study. We used multicolor flow cytometry on frozen peripheral blood mononuclear cells to determine iNKT subset frequencies, the levels of coinhibitory 2B4 expression, and intracellular interferon-gamma (IFN-gamma) production. CD1d tetramer was used to characterize iNKT cells. Results: We report significantly lower level of 2B4 expression on bulk LTNPs iNKT cells and on their CD4 subsets compared with HIV progressors. Furthermore, the iNKT cells from LTNPs produced higher amount of IFN-gamma than HIV progressors as detected by intracellular cytokine staining. Interestingly, the frequency of 2B4(+)iNKT cells of progressors but not LTNPs significantly correlates with CD4 T-cell count, HIV viral load, and IFN-gamma(+)production by iNKT cells. Conclusion: Our results suggest that in addition to suppressed HIV replication, diminished 2B4 expression and associated coinhibitory signaling, and substantial production of IFN-gamma could contribute to preserved iNKT cell phenotype in LTNPs.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS , 2020. Vol. 85, no 1, p. 73-78
Keywords [en]
iNKT cells; CD4; HIV; LTNP; IFN-gamma
National Category
Immunology
Identifiers
URN: urn:nbn:se:liu:diva-170664DOI: 10.1097/QAI.0000000000002399ISI: 000571130000016PubMedID: 32796294OAI: oai:DiVA.org:liu-170664DiVA, id: diva2:1477697
Note

Funding Agencies|University of Malaya Research Grant of the Health and Translational Medicine Cluster [RG501-13HTM]; European Molecular Biology Organization (EMBO) Short-Term Fellowship; Deutsches Zentrum fur Infektions forschung [DZIF TTU HIV 04.802]; High Impact Research Grant of the Ministry of Higher Education (MoHE) Malaysia [HIRGA E000001-20001]; Swedish Research CouncilSwedish Research Council [AI52731]; Swedish Physicians against AIDS Research Foundation; Swedish International Development Cooperation Agency; SIDA SARC; VINNMER for VinnovaVinnova; Linkoping University Hospital Research Fund; CALF; Swedish Society of Medicine; Department of Science and TechnologyScience and Engineering Research Board, Government of India [CRG/2019/006096]; Xiamen University Malaysia Research Funding (XMUMRF) [XMUMRF/2018C2/ILAB/0001]

Available from: 2020-10-19 Created: 2020-10-19 Last updated: 2020-10-19

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