{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T06:59:39Z","timestamp":1790492379565,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["ZAI001029"],"award-info":[{"award-number":["ZAI001029"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>African green monkeys (AGMs), Chlorocebus pygerythrus, are a natural host for a lentivirus related to HIV, SIV. SIV-infected AGMs rarely progress to AIDS despite robust viral replication. Though multiple mechanisms are involved, a primary component is the animals\u2019 ability to downregulate CD4 expression on mature CD4+ Th cells, rendering these cells resistant to infection by SIV. These CD8\u03b1\u03b1+ T cells retain functional characteristics of CD4+ Th cells while simultaneously acquiring abilities of cytotoxic CD8\u03b1\u03b2+ T cells. To determine mechanisms underlying functional differences between T cell subsets in AGMs, chromatin accessibility in purified populations was determined by assay for transposase-accessible chromatin sequencing. Differences in chromatin accessibility alone were sufficient to cluster cells by subtype, and accessibility at the CD4 locus reflected changes in CD4 expression. DNA methylation at the CD4 locus also correlated with inaccessible chromatin. By associating accessible regions with nearby genes, gene expression was found to correlate with accessibility changes. T cell and immune system activation pathways were identified when comparing regions that changed accessibility from CD4+ T cells to CD8\u03b1\u03b1+ T cells. Different transcription factor binding sites are revealed as chromatin accessibility changes, and these differences may elicit downstream changes in differentiation. This comprehensive description of the epigenetic landscape of AGM T cells identified genes and pathways that could have translational value in therapeutic approaches recapitulating the protective effects CD4 downregulation.<\/jats:p>","DOI":"10.4049\/jimmunol.2200109","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T15:20:03Z","timestamp":1657812003000},"page":"337-345","source":"Crossref","is-referenced-by-count":7,"title":["Epigenetic Reprogramming Leads to Downregulation of CD4 and Functional Changes in African Green Monkey Memory CD4+ T Cells"],"prefix":"10.1093","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6306-4584","authenticated-orcid":false,"given":"Andrew R","family":"Rahmberg","sequence":"first","affiliation":[{"name":"Barrier Immunity Section, Lab of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tovah E","family":"Markowitz","sequence":"additional","affiliation":[{"name":"NIAID Collaborative Bioinformatics Resource, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD"},{"name":"Axle Informatics , Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph C","family":"Mudd","sequence":"additional","affiliation":[{"name":"Tulane National Primate Research Center, Division of Immunology, Tulane University , New Orleans, LA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Nonhuman Primate Virology Section, Lab of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8357-2984","authenticated-orcid":false,"given":"Jason M","family":"Brenchley","sequence":"additional","affiliation":[{"name":"Barrier Immunity Section, Lab of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,7,15]]},"reference":[{"key":"2025021008210344900_r1","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1126\/science.1193550","article-title":"Island biogeography reveals the deep history of SIV","volume":"329","author":"Worobey","year":"2010","journal-title":"Science"},{"key":"2025021008210344900_r2","doi-asserted-by":"crossref","first-page":"4868","DOI":"10.1128\/JVI.80.10.4868-4877.2006","article-title":"Comparison of simian immunodeficiency virus SIVagmVer replication and CD4+ T-cell dynamics in vervet and sabaeus African green monkeys","volume":"80","author":"Goldstein","year":"2006","journal-title":"J. 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