Anticytomegalovirus CD4+T Cells Are Associated With Subclinical Atherosclerosis in Persons With HIV

Celestine N. Wanjalla, Mona Mashayekhi, Samuel Bailin, Curtis L. Gabriel, Leslie M. Meenderink, Tecla Temu, Daniella T. Fuller, Liang Guo, Kenji Kawai, Renu Virmani, Cathy Jenkins, Chike O. Abana, Christian M. Warren, Rama Gangula, Rita Smith, Meena S. Madhur, Aloke V. Finn, Alexander H. Gelbard, Yan Ru Su, Matthew J. TyskaSpyros A. Kalams, David G. Harrison, Simon A. Mallal, Tarek S. Absi, Joshua A. Beckman, John R. Koethe

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Objective: Persons with HIV have double the risk of developing cardiovascular disease compared with the general population. A persistent and heightened immune response to cytomegalovirus coinfection may be one contributing factor, but the relationship between cytomegalovirus replication, virus-specific immune cells, and plaque burden is unclear. Approach and Results: We assessed the relationship between CD4+T-cell subsets and carotid plaque burden in a cohort of 70 HIV-positive participants with sustained viral suppression on a single antiretroviral regimen and without known cardiovascular disease. We evaluated relationships between immune parameters, carotid plaque burden, and brachial artery flow-mediated vasodilation using multivariable linear and logistic regression models. We found that participants with carotid plaque had increased circulating CX3CR1+∼GPR56+∼CD57+(ie, C∼G∼C)+CD4+T cells (P=0.03), which is a marker combination associated with antiviral and cytotoxic responses. In addition, a median of 14.4% (IQR, 4.7%-32.7%) of the C∼G∼C+CD4+T-cells expressed antigen receptors that recognized a single cytomegalovirus glycoprotein-B epitope. Using immunofluorescence staining, we found that CX3CR1+CD4+T cells were present in coronary plaque from deceased HIV-positive persons. C∼G∼C+CD4+T cells were also present in cells isolated from the aorta of HIV-negative donors. Conclusions: HIV-positive persons with carotid atheroma have a higher proportion of circulating CD4+T-cells expressing the C∼G∼C surface marker combination associated with antiviral and cytotoxic responses. These cells can be cytomegalovirus-specific and are also present in the aorta.

Original languageEnglish (US)
Pages (from-to)1459-1473
Number of pages15
JournalArteriosclerosis, thrombosis, and vascular biology
Volume41
Issue number4
DOIs
StatePublished - Apr 1 2021
Externally publishedYes

Keywords

  • HIV
  • atherosclerosis
  • cardiovascular diseases
  • cytomegalovirus
  • inflammation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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