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. 2021 Nov 16;224(9):1599-1604.
doi: 10.1093/infdis/jiab155.

Correlation Between TIGIT Expression on CD8+ T Cells and Higher Cytotoxic Capacity

Jana Blazkova  1 , Erin D Huiting  1 , Arun Kumar Boddapati  2   3 , Victoria Shi  1 , Emily J Whitehead  1 , Jesse S Justement  1 , Jeffrey L Nordstrom  4 , Susan Moir  1 , Justin Lack  2   3 , Tae-Wook Chun  1
Affiliations

Correlation Between TIGIT Expression on CD8+ T Cells and Higher Cytotoxic Capacity

Jana Blazkova et al. J Infect Dis. .

Abstract

Persistent exposure to antigen leads to T-cell exhaustion and immunologic dysfunction. We examined the immune exhaustion markers T cell immunoglobulin and ITIM domain (TIGIT) and programmed cell death protein 1 (PD-1) in human immunodeficiency virus (HIV)-infected and healthy individuals and the relationship with cytotoxic CD8+ T-lymphocyte activity. Frequencies of TIGIT but not PD-1 were positively correlated with CD8+ T-lymphocyte activity in HIV-aviremic and healthy individuals; however, there was no correlation in HIV-viremic individuals. Transcriptome analyses revealed up-regulation of genes associated with antiviral immunity in TIGIT+CD8+ versus TIGIT-CD8+ T cells. Our data suggest that TIGIT+CD8+ T cells do not necessarily represent a state of immune exhaustion and maintain an intrinsic cytotoxicity in HIV-infected individuals.

Keywords: TIGIT; cytotoxic T lymphocytes; human immunodeficiency virus; immune exhaustion.

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Figures

Figure 1.
Figure 1.
Phenotypic and functional analyses of CD8+ T cells expressing markers of immune exhaustion. A, Peripheral blood mononuclear cells of human immunodeficiency virus (HIV)–infected aviremic (n = 81), HIV-infected viremic (n = 42), and healthy individuals (n = 74) were subjected to flow cytometry to determine the levels of T cell immunoglobulin and ITIM domain (TIGIT)+CD8+, programmed cell death protein 1 (PD-1)+CD8+, and TIGIT+PD-1+CD8+ T cells. Black vertical lines represent minimum to maximum data points; black horizontal lines, interquartile range and median values. P values were determined using the Mann-Whitney test. B, Enriched CD8+ T cells of HIV-infected aviremic (n = 61) and viremic (n = 21) and healthy individuals (n = 40) were cocultured with CEM-IIIB cells in the presence of a HIV-specific dual-affinity retargeting (DART) molecule or a control molecule. The cytotoxic activity of CD8+ T cells was determined by the percentage of dead CEM-IIIB cells, using a nucleic acid dye and flow cytometry. The relationship between the CD8+ T-cell–mediated killing and the level of TIGIT+CD8+, PD-1+CD8+, and TIGIT+PD-1+CD8+ T cells is shown for all study groups. Correlations were determined using the Spearman method.
Figure 2.
Figure 2.
Transcriptome analyses of TIGIT+CD8+ and TIGIT−CD8+ T-cell subsets. Enriched TIGIT+CD8+ and TIGIT−CD8+ T cells from human immunodeficiency virus (HIV)–aviremic (n = 8), HIV-viremic (n = 6), and healthy individuals (n = 15) were subjected to RNA microarray analysis. A, Principal component analysis. B, Venn diagram of genes differentially expressed in TIGIT+CD8+ versus TIGIT−CD8+ T cells of the 3 study groups. Numbers of genes commonly expressed among the study groups are indicated. C, Hierarchically clustered heat map of 180 differentially expressed genes between TIGIT+CD8+ and TIGIT−CD8+ T-cell subsets in HIV-aviremic and healthy individuals. Top categories of gene ontology (GO) analyses are listed. D, Hierarchically clustered heat map of differentially expressed genes in the TIGIT+CD8+ T-cell subsets of HIV-viremic versus HIV-aviremic and healthy individuals. Differences in relative levels of gene expression (z score) are indicated in color, where red indicates up-regulation and blue, down-regulation. Abbreviation: BH, Benjamini-Hochberg; FDR, false discovery rate; ID, identifier.
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References

    1. Volberding PA, Deeks SG. Antiretroviral therapy and management of HIV infection. Lancet 2010; 376:49–62. - PubMed
    1. Chun TW, Moir S, Fauci AS. HIV reservoirs as obstacles and opportunities for an HIV cure. Nat Immunol 2015; 16:584–9. - PubMed
    1. Sengupta S, Siliciano RF. Targeting the latent reservoir for HIV-1. Immunity 2018; 48:872–95. - PMC - PubMed
    1. Collins DR, Gaiha GD, Walker BD. CD8+ T cells in HIV control, cure and prevention. Nat Rev Immunol 2020; 20:471–82. - PMC - PubMed
    1. Wherry EJ, Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol 2015; 15:486–99. - PMC - PubMed

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