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. 2020 Mar 20:10:113.
doi: 10.3389/fcimb.2020.00113. eCollection 2020.

Combined Effects of HLA-B*57/5801 Elite Suppressor CD8+ T Cells and NK Cells on HIV-1 Replication

Megan E May  1 , Christopher W Pohlmeyer  1 , Abena K Kwaa  1 , Madeleine C Mankowski  1 , Justin R Bailey  1 , Joel N Blankson  1
Affiliations

Combined Effects of HLA-B*57/5801 Elite Suppressor CD8+ T Cells and NK Cells on HIV-1 Replication

Megan E May et al. Front Cell Infect Microbiol. .

Abstract

Elite controllers or suppressors (ES) are HIV-1 infected individuals who maintain undetectable viral loads without anti-retroviral therapy. The HLA-B*57 allele is overrepresented in ES suggesting a role for HIV-specific CD8+ T cells in immune control. Natural killer (NK) cells also play a role in controlling viral replication, and genetic studies demonstrate that specific combinations of killer cell immunoglobulin-like receptor (KIR) alleles and HLA subtypes including HLA-B*57 correlate with delayed progression to AIDS. While prior studies have shown that both HIV-specific CD8+ T cells and NK cells can inhibit viral replication in vitro, the interaction between these two effector cells has not been studied. We performed in vitro suppression assays using CD8+ T cells and NK cells from HLA-B*57 ES either alone or in combination with each other. We found no evidence of antagonism or synergy between the CD8+ T cells and NK cells, suggesting that they have independent mechanisms of inhibition in vitro. Our data has implications for combined immunotherapy with CD8+ T cells and NK cells in HIV cure strategies.

Keywords: CD8+ T cells; HIV-1; NK cells; viral replication; viral suppression.

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Figures

Figure 1
Figure 1
Scheme of the suppression assay used in this study.
Figure 2
Figure 2
Gating strategy used in this manuscript. CD8+ T cell suppression was calculated as [1–(%GFP + CD4+ T cells cultured with effectors)/(%GFP + CD4+ T cells without effectors)] × 100. For CD8+ T cells this was [1–3/26] × 100 or 88.4% suppression. For NK cells this was [1–14/26] × 100 or 46.2% suppression.
Figure 3
Figure 3
Viral suppression induced by CD8+ T cells, NK cells, and a combination of the two effector cells at the indicated effector to target ratios for each individual. The bar is set to the mean value from 3 replicates per subject with the exception of VC10 where a single replicate was run due to limited numbers of cells. Error bars are the standard error of the mean.
Figure 4
Figure 4
Composite viral suppression by CD8+ T cells, NK cells, and a combination of the two effector cells (A). The mean value for each subject is plotted. A comparison of the observed suppression by the combination of NK cells and CD8+ T cells (blue columns) to the degree of suppression predicted by the Bliss independence model (red columns) is shown for each individual (B) and for the cohort (C). The bar is set to the mean value from 3 replicates per subject. Error bars represent the standard deviation from the mean.
See this image and copyright information in PMC

References

    1. Alter G., Martin M. P., Teigen N., Carr W. H., Suscovich T. J., Schneidewind A., et al. . (2007). Differential natural killer cell-mediated inhibition of HIV-1 replication based on distinct KIR/HLA subtypes. J. Exp. Med. 204, 3027–3036. 10.1084/jem.20070695 - DOI - PMC - PubMed
    1. Andrews D. M., Estcourt M. J., Andoniou C. E., Wikstrom M. E., Khong A., Voigt V., et al. . (2010). Innate immunity defines the capacity of antiviral T cells to limit persistent infection. J. Exp. Med. 207, 1333–1343. 10.1084/jem.20091193 - DOI - PMC - PubMed
    1. Apps R., Del Prete G. Q., Chatterjee P., Lara A., Brumme Z. L., Brockman M. A., et al. . (2016). HIV-1 Vpu mediates HLA-C downregulation. Cell Host Microbe 19, 686–695. 10.1016/j.chom.2016.04.005 - DOI - PMC - PubMed
    1. Betts M. R., Nason M. C., West S. M., De Rosa S. C., Migueles S. A., Abraham J., et al. . (2006). HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood 107, 4781–4789. 10.1182/blood-2005-12-4818 - DOI - PMC - PubMed
    1. Bliss C. I. (1939). The toxicity of poisons applied jointly. Ann. Appl. Biol. 1939, 585–615. 10.1111/j.1744-7348.1939.tb06990.x - DOI

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