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Chronic HIV Infection Exacerbates Cellular Aging Markers in Isolated T cell Subsets
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Reported by Jules Levin
CROI 2015 Feb 23-26, Seattle, WA
Anthony Y.Y. Hsieha,b, Beheroze Satthaa, Helene C.F. Cotea,b and the CIHR team grant for the CIHR Team in Cellular Aging and HIV Comorbidities in Women and Children (CARMA cohort)
aDepartment of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada; bCentre for Blood Research, Vancouver, BC, Canada
program abstract
Chronic HIV Infection Exacerbates Cellular Aging Markers in Isolated T-Cell Subsets
Anthony Hsieh; Beheroze Sattha; Helene Cote
CIHR Team in Cellular Aging and HIV Comorbidities in Women and Children (CARMA cohort) University of British Columbia, Vancouver, Canada
Background: Shorter telomere in the expanded senescent CD8+ T cell compartment is an age-related immunologic abnormality reported in a small cohort study of people living with HIV.This immune defect, along with imbalance in CD4+ and CD8+ T cell distributions may link chronic HIV infection with premature age-related comorbidities, even in people treated with combination ART (cART).Little is known about markers such as telomere length (TL) and mitochondrial DNA apparent oxidative damage (mtDNA AOD) in isolated immune compartments during HIV infection.Our objective was to characterize these aging markers in CD4+ and CD8+ T cell subsets, and explore the possible role of HIV/cART on modulating immune aging.We hypothesized that HIV infection and factors such as viral load or time since diagnosis would be associated with skewed immune aging markers.
Methods: In this pilot study, live PBMCs were obtained from 33 HIV+ subjects and 10 HIV- controls enrolled in the CARMA cohort study.FACS was used to isolate CD4+, proliferative CD8+ CD28+, and senescent CD8+ CD28- T cells, as well as CD19+ B cells.Relative TL and mtDNA AOD were measured in all cell subsets with sufficient cell count using qPCR.Results were compared using SpearmanŐs correlation, two-tailed Mann-Whitney tests, and ANCOVA.
Results: As expected, a decreased CD4+/CD8+ T cell ratio (n=43, median 0.24 vs.1.75, p<0.001) and an expanded senescent CD8+CD28- T cell subset (n=43, 39 vs 17% of total T cells, p=0.02) were observed in the HIV+ group compared to the HIV- group.HIV infection was associated with shorter TL in proliferative CD8+CD28+ T cells (n=27, 3.35 vs.3.73, p=0.02), but not in CD8+CD28- or CD4+ T cells after adjusting for age.Within the entire cohort, older age was associated with shorter TL in CD4+ (n=26, R=-0.45, p=0.02), and proliferative CD8+CD28+ (n=27, R=-0.47, p=0.01) but not senescent CD8+CD28- cells (R=-0.06).MtDNA AOD correlated with lifetime cART duration in both CD8+CD28- and CD8+CD28+ T cells (n=22, R=0.53, p=0.01, and n=22, R=0.45, p=0.04).No relationship was seen between current HIV viral load, CD4 current or nadir, or time since diagnosis, and the aging markers assayed here.
Conclusions: Taken together, these results suggest a potential relationship between HIV infection and shorter TL in proliferative CD8+ T cells.In contrast, cART duration was related to mtDNA oxidative damage in CD8+ T cells, suggesting that cumulative exposure may play a role in mitochondrial aging in this immune compartment.
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