Multivariate Computational Analysis of Gamma Delta T Cell Inhibitory Receptor Signatures Reveals the Divergence of Healthy and ART-Suppressed HIV+ Aging
Even with effective viral control, HIV-infected individuals are at a higher risk for morbidities associated with older age than the general population, and these serious non-AIDS events (SNAEs) track with plasma inflammatory and coagulation markers. The cell subsets driving inflammation in aviremic...
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| Format: | Article |
| Language: | English |
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Frontiers Media SA
2020
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| Online Access: | https://hdl.handle.net/1721.1/126063 |
| _version_ | 1826212553950232576 |
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| author | Starchenko, Alina Proctor, Elizabeth A Lauffenburger, Douglas A |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Starchenko, Alina Proctor, Elizabeth A Lauffenburger, Douglas A |
| author_sort | Starchenko, Alina |
| collection | MIT |
| description | Even with effective viral control, HIV-infected individuals are at a higher risk for morbidities associated with older age than the general population, and these serious non-AIDS events (SNAEs) track with plasma inflammatory and coagulation markers. The cell subsets driving inflammation in aviremic HIV infection are not yet elucidated. Also, whether ART-suppressed HIV infection causes premature induction of the inflammatory events found in uninfected elderly or if a novel inflammatory network ensues when HIV and older age co-exist is unclear. In this study we measured combinational expression of five inhibitory receptors (IRs) on seven immune cell subsets and 16 plasma markers from peripheral blood mononuclear cells (PBMC) and plasma samples, respectively, from a HIV and Aging cohort comprised of ART-suppressed HIV-infected and uninfected controls stratified by age (≤35 or ≥50 years old). For data analysis, multiple multivariate computational algorithms [cluster identification, characterization, and regression (CITRUS), partial least squares regression (PLSR), and partial least squares-discriminant analysis (PLS-DA)] were used to determine if immune parameter disparities can distinguish the subject groups and to investigate if there is a cross-impact of aviremic HIV and age on immune signatures. IR expression on gamma delta (γδ) T cells exclusively separated HIV+ subjects from controls in CITRUS analyses and secretion of inflammatory cytokines and cytotoxic mediators from γδ T cells tracked with TIGIT expression among HIV+ subjects. Also, plasma markers predicted the percentages of TIGIT+ γδ T cells in subjects with and without HIV in PSLR models, and a PLS-DA model of γδ T cell IR signatures and plasma markers significantly stratified all four of the subject groups (uninfected younger, uninfected older, HIV+ younger, and HIV+ older). These data implicate γδ T cells as an inflammatory driver in ART-suppressed HIV infection and provide evidence of distinct "inflamm-aging" processes with and without ART-suppressed HIV infection. |
| first_indexed | 2024-09-23T15:25:03Z |
| format | Article |
| id | mit-1721.1/126063 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T15:25:03Z |
| publishDate | 2020 |
| publisher | Frontiers Media SA |
| record_format | dspace |
| spelling | mit-1721.1/1260632022-10-02T02:39:41Z Multivariate Computational Analysis of Gamma Delta T Cell Inhibitory Receptor Signatures Reveals the Divergence of Healthy and ART-Suppressed HIV+ Aging Starchenko, Alina Proctor, Elizabeth A Lauffenburger, Douglas A Massachusetts Institute of Technology. Department of Biological Engineering Even with effective viral control, HIV-infected individuals are at a higher risk for morbidities associated with older age than the general population, and these serious non-AIDS events (SNAEs) track with plasma inflammatory and coagulation markers. The cell subsets driving inflammation in aviremic HIV infection are not yet elucidated. Also, whether ART-suppressed HIV infection causes premature induction of the inflammatory events found in uninfected elderly or if a novel inflammatory network ensues when HIV and older age co-exist is unclear. In this study we measured combinational expression of five inhibitory receptors (IRs) on seven immune cell subsets and 16 plasma markers from peripheral blood mononuclear cells (PBMC) and plasma samples, respectively, from a HIV and Aging cohort comprised of ART-suppressed HIV-infected and uninfected controls stratified by age (≤35 or ≥50 years old). For data analysis, multiple multivariate computational algorithms [cluster identification, characterization, and regression (CITRUS), partial least squares regression (PLSR), and partial least squares-discriminant analysis (PLS-DA)] were used to determine if immune parameter disparities can distinguish the subject groups and to investigate if there is a cross-impact of aviremic HIV and age on immune signatures. IR expression on gamma delta (γδ) T cells exclusively separated HIV+ subjects from controls in CITRUS analyses and secretion of inflammatory cytokines and cytotoxic mediators from γδ T cells tracked with TIGIT expression among HIV+ subjects. Also, plasma markers predicted the percentages of TIGIT+ γδ T cells in subjects with and without HIV in PSLR models, and a PLS-DA model of γδ T cell IR signatures and plasma markers significantly stratified all four of the subject groups (uninfected younger, uninfected older, HIV+ younger, and HIV+ older). These data implicate γδ T cells as an inflammatory driver in ART-suppressed HIV infection and provide evidence of distinct "inflamm-aging" processes with and without ART-suppressed HIV infection. National Institutes of Health (U.S.) (Grant R01-DK108056) National Institutes of Health (U.S.) (Grant R01 DA041748-01) National Institutes of Health (U.S.) (Grant R01 AG060890-01) National Institutes of Health (U.S.) (Grant 1UL1TR001430) National Institute of General Medical Sciences (U.S.) (Grant R44GM117914) United States. Army Research Office. Institute for Collaborative Biotechnologies (Grant W911NF-09-0001) 2020-07-07T15:50:55Z 2020-07-07T15:50:55Z 2018-12 2020-03-12T16:37:01Z Article http://purl.org/eprint/type/JournalArticle 1664-3224 https://hdl.handle.net/1721.1/126063 Belkina, Anna C. et al. “Multivariate Computational Analysis of Gamma Delta T Cell Inhibitory Receptor Signatures Reveals the Divergence of Healthy and ART-Suppressed HIV+ Aging.” Frontiers in immunology, vol. 9, 2018, 2783 © 2018 The Author(s) en 10.3389/FIMMU.2018.02783 Frontiers in immunology Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Frontiers Media SA Frontiers |
| spellingShingle | Starchenko, Alina Proctor, Elizabeth A Lauffenburger, Douglas A Multivariate Computational Analysis of Gamma Delta T Cell Inhibitory Receptor Signatures Reveals the Divergence of Healthy and ART-Suppressed HIV+ Aging |
| title | Multivariate Computational Analysis of Gamma Delta T Cell Inhibitory Receptor Signatures Reveals the Divergence of Healthy and ART-Suppressed HIV+ Aging |
| title_full | Multivariate Computational Analysis of Gamma Delta T Cell Inhibitory Receptor Signatures Reveals the Divergence of Healthy and ART-Suppressed HIV+ Aging |
| title_fullStr | Multivariate Computational Analysis of Gamma Delta T Cell Inhibitory Receptor Signatures Reveals the Divergence of Healthy and ART-Suppressed HIV+ Aging |
| title_full_unstemmed | Multivariate Computational Analysis of Gamma Delta T Cell Inhibitory Receptor Signatures Reveals the Divergence of Healthy and ART-Suppressed HIV+ Aging |
| title_short | Multivariate Computational Analysis of Gamma Delta T Cell Inhibitory Receptor Signatures Reveals the Divergence of Healthy and ART-Suppressed HIV+ Aging |
| title_sort | multivariate computational analysis of gamma delta t cell inhibitory receptor signatures reveals the divergence of healthy and art suppressed hiv aging |
| url | https://hdl.handle.net/1721.1/126063 |
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