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IL-6 and CD8 Senescence Independently Associate With Atherosclerosis in Treated HIV
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Reported by Jules Levin
CROI 2015 Feb 23-26, Seattle, WA
Denise Hsu1, Zonghui Hu1, Irini Sereti1, Courtney Carroll2, Kristinalisa Maka2, Steven Deeks2, S. Kalapus2, Priscilla Hsue2, Adam Rupert3
1 National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States;2 University of California San Francisco, San Francisco, California, United States;3 Leidos Biomedical Research, Inc, Frederick, Maryland, United States
program abstract
Background: Increased cardiovascular (CV) risk persists among patients with treated HIV disease, and chronic immune activation is thought to contribute to this excess risk. Carotid intima-media thickness (CIMT) assesses atherosclerotic burden and predicts future CV events. We studied the immunologic correlates of CIMT in patients on ART with suppressed viral load (VL).
Methods: Cryopreserved mononuclear cells and plasma from the SCOPE study were used to evaluate T-cell and monocyte activation by flow cytometry and soluble markers of inflammation/coagulation by ELISA-based methods. CIMT was measured by high resolution ultrasound. Mean CIMT was calculated as the average of 12 segments (near and far wall of the common, internal, and bifurcation region of the right and left carotid arteries). Plaque was defined as a focal region of IMT>1.5mm. Associations between CIMT and immunologic markers were assessed by Spearman's rank correlation and multivariate regression adjusting for traditional CV risk factors and CD4 count. Associations between the presence of plaque and immunologic markers were evaluated by Wilcoxon test.
Results: Participants (N=132) were on ART with VL In multivariate regression adjusting for traditional CV risk factors and CD4 count, higher levels of plasma IL-6 (PLevels of D-dimer, CRP, sCD14, sCD163, HLA-DR+CD38+CD8+T cells and CD16+ monocytes were not associated with common carotid or mean CIMT or plaque after adjusting for traditional CV risk factors and CD4 count.
Conclusions: In patients on ART with suppressed VL, higher plasma IL6 and CCR5 expression on monocytes and higher % of CD57+ cells in CD28-CD8+T cells were independently associated with thicker CIMT after adjusting for CVD risk factors and CD4 count. Dysfunction of innate immune cells and CD8 T cell senescence likely contribute to atherosclerosis in the setting of treated and suppressed HIV.
from Jules: The expression of CD57 correlates with senescence in human CD8 T cells....http://www.bloodjournal.org/content/bloodjournal/116/19/3865.full.pdf?sso-checked=true.......Similar to NK cells, CD8 T cells are crucial to the recognition and clearance of virus-infected cells. Chronic stimulation of T cells, which occurs during rheumatoid arthritis, multiple myeloma, and cytomegalovirus and HIV infections, and after bone marrow transplantation, can result in the development of CD8 T cells that are capable of cytokine secretion yet are incapable of cell division.13,14 Such failure to proliferate is generally attributed to replicative senescence or "clonal exhaustion" resulting from continual stimulation by antigens and/or cytokines. The expression of CD57 correlates with senescence in human CD8
_ T cells.......IL-6....
http://circ.ahajournals.org/content/101/15/1767.full
......http://www.natap.org/2013/CROI/croi_113.htm
......http://www.hindawi.com/journals/jir/2012/467154/
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