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- Title
Proximity of Cytomegalovirus-Specific CD8<sup>+</sup> T Cells to Replicative Senescence in Human Immunodeficiency Virus-Infected Individuals.
- Authors
Heath, John Joseph; Fudge, Neva Jennifer; Gallant, Maureen Elizabeth; Grant, Michael David
- Abstract
Antiretroviral therapy (ART) effectively extends the life expectancy of human immunodeficiency virus (HIV)-infected individuals; however, agerelated morbidities have emerged as major clinical concerns. In this context, coinfection with cytomegalovirus (CMV) accelerates immune senescence and elevates risk for other agerelated morbidities, possibly through increased inflammation. We investigated potential relationships between CMV memory inflation, immune senescence, and inflammation by measuring markers of inflammation and telomere lengths of different lymphocyte subsets in HIVinfected individuals seropositive for antiCMV antibodies. Our study cohort consists mainly of middle aged men who have sex with men (MSM) and heterosexuals who are stable under longterm ART. Median levels of IL6, TNFα, and CRP were significantly higher in those coinfected with CMV. Lymphocyte telomere length in general correlated with age, but for 32/32 subjects tested, there was a consistent hierarchy of telomere lengths with CD8+ T cells' shorter than the general lymphocyte population, CD57+CD8+ T cells' shorter than CD8+ T cells' and CMVspecific CD57+CD8+ T cells' the shortest of all. Telomeres of HIVspecific CD8+ T cells were longer than those of CMVspecific CD8+ T cells in all cases tested and over 10 years, CMV-specific CD8+ T cell telomeres of two HIVinfected individuals eroded faster than those of HIVspecific CD8+ T cells. These data indicate that CMVspecific CD8+ T cells of HIVinfected individuals are the lymphocytes closest to telomereimposed replicative senescence. Exhaustive proliferation of CMVspecific CD8+ T cells in HIVinfected individuals is a potential source of senescent lymphocytes affecting systemic immune function and inflammation.
- Subjects
CYTOMEGALOVIRUSES; HIV infections -- Immunological aspects; ANTIRETROVIRAL agents
- Publication
Frontiers in Immunology, 2018, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2018.00201