Accelerated Aging in HIV/AIDS: Novel Biomarkers of Senescent Human CD8+ T Cells

Clinical evaluation of immune reconstitution and health status during HIV-1 infection and anti-retroviral therapy (ART) is largely based on CD4+ T cell counts and viral load, measures that fail to take into account the CD8+ T cell subset, known to show features of accelerated aging in HIV disease. H...

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Vydané v:	PloS one Ročník 8; číslo 5; s. e64702
Hlavní autori:	Chou, Jennifer P., Ramirez, Christina M., Wu, Jennifer E., Effros, Rita B.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Public Library of Science 22.05.2013 Public Library of Science (PLoS)
Predmet:	Acquired immune deficiency syndrome Adenosine Adenosine deaminase Aging Aging - pathology AIDS AIDS treatment Analysis Antiretroviral agents Antiretroviral therapy Base Sequence Bioindicators Biological markers Biology Biomarkers Biomarkers - metabolism CD38 antigen CD4 antigen CD8 antigen CD8-Positive T-Lymphocytes - pathology Cell activation Cell culture Cell cycle Cell survival Cellular Senescence Development and progression DNA methylation DNA Primers Flow Cytometry Gene expression Genes Genetic aspects Glucose metabolism Health aspects Histocompatibility antigen HLA HIV HIV Infections - pathology Human immunodeficiency virus Humans Immune reconstitution Immune status Immunology Infection Infections Laboratories Leucine Lymphocytes Lymphocytes T Medicine Middle Aged Novels Pathology Population Real-Time Polymerase Chain Reaction Senescence Studies Synergism T cells Telomerase Type 2 diabetes Los Angeles California United States > US California
ISSN:	1932-6203, 1932-6203
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Shrnutí:	Clinical evaluation of immune reconstitution and health status during HIV-1 infection and anti-retroviral therapy (ART) is largely based on CD4+ T cell counts and viral load, measures that fail to take into account the CD8+ T cell subset, known to show features of accelerated aging in HIV disease. Here, we compare adenosine deaminase (ADA), glucose uptake receptor 1 (GLUT1), and leucine-rich repeat neuronal 3 (LRRN3) to CD38 expression and telomerase activity, two strong predictors of HIV disease progression. Our analysis revealed that reduced ADA, telomerase activity and LRRN3 gene expression were significantly associated with high CD38 and HLA-DR in CD8+ T cells, with % ADA+ cells being the most robust predictor of CD8+ T cell activation. Our results suggest that ADA, LRRN3 and telomerase activity in CD8+ T cells may serve as novel, clinically relevant biomarkers of immune status in HIV-1 infection, specifically by demonstrating the degree to which CD8+ T cells have progressed to the end stage of replicative senescence. Since chronological aging itself leads to the accumulation of senescent CD8+ T cells, the prolonged survival and resultant increased age of the HIV+ population may synergize with the chronic immune activation to exacerbate both immune decline and age-associated pathologies. The identification and future validation of these new biomarkers may lead to fresh immune-based HIV treatments.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Undefined-3 Competing Interests: The authors have declared that no competing interests exist. Conceived and designed the experiments: JPC RBE. Performed the experiments: JPC JEW. Analyzed the data: JPC CMR. Contributed reagents/materials/analysis tools: JPC CMR RBE. Wrote the paper: JPC RBE.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0064702