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  1. Ahmad F, Shankar EM, Yong YK, Tan HY, Ahrenstorf G, Jacobs R, et al.
    Front Immunol, 2017;8:338.
    PMID: 28396665 DOI: 10.3389/fimmu.2017.00338
    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) naïve, ART-treated, and elite controllers (ECs). We report on exaggerated 2B4 expression on iNKT cells of HIV-infected treatment-naïve 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 ART-naïve individuals were defective in their ability to produce intracellular IFN-γ. Together, our results suggest that the levels of 2B4 expression and the downstream co-inhibitory signaling events may contribute to impaired iNKT cell responses.
    Matched MeSH terms: Antigens, CD1d
  2. Ansari AW, Ahmad F, Shankar EM, Kong YY, Tan HY, Jacobs R, et al.
    PMID: 32398557 DOI: 10.1097/QAI.0000000000002399
    BACKGROUND: We have previously shown an association of elevated co-inhibitory 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 non-progressors (LTNPs) and progressors.

    METHODS: Anti-retroviral therapy (ART) naïve HIV-seropositive individuals (progressors, n=16) and long-term non-progressors (LTNPs, n=10) were recruited for this study. We employed multi-color flow cytometry on frozen peripheral blood mononuclear cells (PBMCs) to determine iNKT subset frequencies, the levels of co-inhibitory 2B4 expression, and intracellular IFN-γ production. CD1d tetramer was used to characterize iNKT cells.

    RESULTS: We report significantly lower level of 2B4 expression on bulk LTNPs iNKT cells as well as on their CD4 subsets compared to HIV progressors. Furthermore, the iNKT cells from LTNPs produced higher amount of IFN-γ than HIV progressors as detected by intracellular cytokine staining. Interestingly, the frequency of 2B4iNKT cells of progressors but not LTNPs significantly correlates with CD4 T cell count, HIV viral load and IFNγ production by iNKT cells.

    CONCLUSION: Our results suggest that in addition to suppressed HIV replication, diminished 2B4 expression and associated co-inhibitory signaling, and substantial production of IFN-γ could contribute to preserved iNKT cell phenotype in LTNPs.

    Matched MeSH terms: Antigens, CD1d
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