Advisory Committee Chair
Olaf Kutsch
Advisory Committee Members
Randy Q Cron
Paul Goepfert
Hui Hu
Chander Raman
Steffanie Sabbaj
Document Type
Dissertation
Date of Award
2023
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
Antiretroviral therapy (ART) has greatly improved the life expectancy of People With HIV (PWH), but despite ART, PWH show signs of chronic immune hyperactivation (CIH), which results in the development of early-onset comorbidities, such as metabolic syndrome, diabetes, cardiovascular complications, neurodegenerative impairment, and can-cer. The underlying causes of CIH are, at best, incompletely understood, with suggested roles of microbial translocation, viral coinfections, T cell imbalances, and persistent HIV replication. Given that the CD4+ T cell population is most affected during acute HIV infec-tion, it is surprising that no T cell populations have been identified as drivers of CIH. Herein, we investigate a possible role of CD151+ T cells as drivers of CIH in PWH. This idea was based on previous findings from our group that demonstrated that CD151+ are hyperresponsive and proinflammatory. In these studies, I show that CD151 expression was largely not associated with the expression of traditional activation markers, such as CD25 or CD38. We demonstrate that CD151+ T cells are responsible for the vast majority of cytokine proinflammatory produc-tion in healthy controls, a phenotype that is maintained in PWH. We next demonstrated that CD151+ T cell frequencies increased with age and function as an immunological clock, which is impaired in PWH and dysfunctional in PWH who develop cancer (PWHc), a de-fined comorbidity selected for this study. Young PWHc were found to already have ex-tremely high CD151+ T cell frequencies, which given the proinflammatory phenotype of these cells, suggests a possible link of CD151+ T cell accumulation with CIH. Using a combination of scRNAseq analysis and multi-parameter flow cytometry, we identify two CD151+ T cell populations that were highly accumulated specifically in PWHc, CD4+CD151+ cytotoxic T cells, and CD8+CD151+ TEMRA cells, two highly proinflam-matory T cell types known to accumulate as a result of chronic viral infections. The results thus suggest that the presence of elevated CD151+ T cell frequencies at a young age could identify PWH at increased risk of comorbid complications and emphasize the role of chron-ic viral infections as drivers of CIH.
Recommended Citation
Perez, Mildred, "Cd151+ T Cell Frequencies As An Immunological Clock That Identifies Premature Immunological Aging In People With Hiv" (2023). All ETDs from UAB. 3520.
https://digitalcommons.library.uab.edu/etd-collection/3520