Abstract
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.
Highlights
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 provide a somewhat incomplete picture of the true functional status of the immune system
Using the Pearson Correlation model, we found that persons with the lowest percentage of adenosine deaminase (ADA) on total CD8+ T cells had the highest number of surface CD38 and HLA-DR molecules, as well as the highest percentage of CD8+ T cells that were positive for both activation markers
The major finding of the current study relates to ADA, which when complexed to CD26 on antigen-presenting cells, constitutes a key costimulatory component of the immunological synapse
Summary
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 provide a somewhat incomplete picture of the true functional status of the immune system. These parameters fail to consider the state of CD8+ T cells, the subset primarily responsible for controlling the infection through lysis of HIV-1-infected cells, release of perforin and granzyme, production of IFN-c and secretion of soluble factors that suppress HIV-1 replication [1,2]. Given the prolonged survival and ‘‘graying’’ of the HIV-infected population, it is possible that the CD8+ T cell defects due to the infection may synergize with similar defects associated with aging, further highlighting the critical need for more precise characterization of this subset
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
