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Neurovirol."],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>HIV-associated neurocognitive disorders (HAND) is hypothesized to be a result of myeloid cell-induced neuro-inflammation in the central nervous system that may be initiated in the periphery, but the contribution of peripheral T cells in HAND pathogenesis remains poorly understood.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We assessed markers of T cell activation (HLA-DR\u2009+\u2009CD38+), immunosenescence (CD57\u2009+\u2009CD28-), and immune-exhaustion (TIM-3, PD-1 and TIGIT) as well as monocyte subsets (classical, intermediate, and non-classical) by flow cytometry in peripheral blood derived from individuals with HIV on long-term stable anti-retroviral therapy (ART). Additionally, normalized neuropsychological (NP) composite test z-scores were obtained and regional brain volumes were assessed by magnetic resonance imaging (MRI). Relationships between proportions of immune phenotypes (of T-cells and monocytes), NP z-scores, and brain volumes were analyzed using Pearson correlations and multiple linear regression models.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Of <jats:italic>N<\/jats:italic>\u2009=\u200951 participants, 84.3% were male, 86.3% had undetectable HIV RNA\u2009&lt;\u200950 copies\/ml, median age was 52 [47, 57] years and median CD4 T cell count was 479 [376, 717] cells\/uL. Higher CD4 T cells expressing PD-1\u2009+\u2009and\/or TIM-3\u2009+\u2009were associated with lower executive function and working memory and higher CD8 T cells expressing PD-1<jats:sup>+<\/jats:sup> and\/or TIM-3<jats:sup>+<\/jats:sup> were associated with reduced brain volumes in multiple regions (putamen, nucleus accumbens, cerebellar cortex, and subcortical gray matter). Furthermore, higher single or dual frequencies of PD-1\u2009+\u2009and TIM-3\u2009+\u2009expressing CD4 and CD8 T-cells correlated with higher CD16\u2009<jats:italic>+<\/jats:italic>\u2009monocyte numbers.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>This study reinforces evidence that T cells, particularly those with immune exhaustion phenotypes, are associated with neurocognitive impairment and brain atrophy in people living with HIV on ART. Relationships revealed between T-cell immune exhaustion and inflammatory in CD16<jats:sup>+<\/jats:sup> monocytes uncover interrelated cellular processes likely involved in the immunopathogenesis of HAND.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s13365-024-01223-w","type":"journal-article","created":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T14:04:55Z","timestamp":1719842695000},"page":"489-499","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Dynamics of peripheral T cell exhaustion and monocyte subpopulations in neurocognitive impairment and brain atrophy in chronic HIV infection"],"prefix":"10.1007","volume":"30","author":[{"given":"Brooks I.","family":"Mitchell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle E.","family":"Yazel Eiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalpana J.","family":"Kallianpur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louie Mar","family":"Gangcuangco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic C.","family":"Chow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lishomwa C.","family":"Ndhlovu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia M.","family":"Shikuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,29]]},"reference":[{"key":"1223_CR1","doi-asserted-by":"crossref","unstructured":"Abassi M, Morawski BM, Nakigozi G, Nakasujja N, Kong X, Meya DB, Robertson K, Gray R, Wawer MJ, Sacktor N, Boulware DR (2017) Cerebrospinal Fluid Biomarkers and HIV-Associated Neurocognitive Disorders in HIV- Infected Individuals in Rakai, Uganda. 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Ndhlovu is supported and reports grants from the NIH under award R01MH130197 and has received consulting fees from work as a scientific advisor for AbbVie, ViiV Healthcare, and Cytodyn and also serves on the Board of Directors of CytoDyn and has financial interests in Ledidi AS all for work outside of the submitted work. All of the other authors have no financial disclosure or conflicts of interest to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}