Assessing the differential impact of chronic CMV and treated HIV infection on CD8+ T-cell differentiation in a matched cohort study: is CMV the key?
Open Access
- 30 June 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in AIDS Research and Therapy
- Vol. 18 (1), 1-9
- https://doi.org/10.1186/s12981-021-00361-z
Abstract
Background: Cytomegalovirus (CMV) infection is one of the main driving forces of T-cell senescence in the general population, whereas its differential impact in people living with HIV (PLWH) is less well characterized. The study explores the effect of latent CMV infection on T-cell subsets, monocyte/macrophages activation markers, and CRP in PLWH on long-term ART.Methods: Cross-sectional cohort study including PLWH on long-term suppressive ART. Individuals of 4 groups (HIV+CMV−, HIV+CMV+, HIV−CMV+, and HIV−CMV−) were matched 1:1:1:1 for age and sex. Immunophenotyping of lymphocyte and T-cell subsets by multicolor flow cytometry was performed in fresh blood samples collected from patients and healthy donors.Results: Both, latent CMV and treated HIV infection were associated with an expansion of CD8 T cells, a reduced CD4/CD8 ratio, and with CD8 T-cell activation with a cumulative effect in CMV/HIV-coinfected individuals. CMV was associated with elevated numbers of late effector and terminally differentiated CD8 T-cells. Compared to CMV monoinfection, CMV/HIV coinfection showed to be associated with lower proportion of CD28−CD8+ T cells expressing CD57 suggesting that HIV preferentially expands CD28−CD57−CD8+ T cells and impedes terminal differentiation of CD28−CD8+ T cells. We could not show any association between HIV or CMV infection status and concentration of CRP and CD163.Conclusions: CMV infection is associated with phenotypic signs of T-cell senescence, promoting exacerbation and persistence of alterations of the T-cell compartment in PLWH on effective ART, which are associated with adverse clinical outcomes and may be an attractive target for therapeutic interventions.Keywords
Funding Information
- Universitätsklinikum Freiburg
This publication has 40 references indexed in Scilit:
- CD28-Negative CD4+ and CD8+ T Cells in Antiretroviral Therapy–Naive HIV-Infected Adults Enrolled in Adult Clinical Trials Group StudiesThe Journal of Infectious Diseases, 2012
- Soluble CD163, a Novel Marker of Activated Macrophages, Is Elevated and Associated With Noncalcified Coronary Plaque in HIV-Infected PatientsThe Journal of Infectious Diseases, 2011
- Old age and anti-cytomegalovirus immunity are associated with altered T-cell reconstitution in HIV-1-infected patientsAIDS, 2011
- Valganciclovir Reduces T Cell Activation in HIV-Infected Individuals With Incomplete CD4+ T Cell Recovery on Antiretroviral TherapyThe Journal of Infectious Diseases, 2011
- Increased HIV-specific CD8+ T-cell cytotoxic potential in HIV elite controllers is associated with T-bet expressionBlood, 2011
- Plasma Levels of Soluble CD14 Independently Predict Mortality in HIV InfectionThe Journal of Infectious Diseases, 2011
- HIV Infection, Inflammation, Immunosenescence, and AgingAnnual Review of Medicine, 2011
- T Cell Activation and Senescence Predict Subclinical Carotid Artery Disease in HIV-Infected WomenThe Journal of Infectious Diseases, 2011
- No Immune Risk Profile among individuals who reach 100 years of age: Findings from the Swedish NONA immune longitudinal studyExperimental Gerontology, 2007
- CD4+ Count–Guided Interruption of Antiretroviral TreatmentThe New England Journal of Medicine, 2006