Inflammation and CMV-associated lymphocyte senescence in chronic HIV infection

Heath, John J. (2018) Inflammation and CMV-associated lymphocyte senescence in chronic HIV infection. Masters thesis, Memorial University of Newfoundland.

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While acute inflammation is important in immune responses to infection, chronic systemic inflammation intrinsically underlies age-associated pathologies. Lifelong cellular turnover equates biological age with long term accumulation of senescent cells, characterized by cell-cycle arrest and a pro-inflammatory senescence-associated secretory phenotype (SASP). Currently, the exact contributions of lymphocytes to the inflammatory landscape seen during aging remains understudied. Cytomegalovirus (CMV) infection creates an inflated, potentially senescent, CD8⁺ T lymphocyte population, often exaggerated in age and in particular, human immunodeficiency virus (HIV) infection. Many living with long-term HIV infection often suffer “premature” age-related illnesses. Frequent rounds of antigen-driven expansion of CMV-specific lymphocytes could introduce a telomere-dependent SASP and a role in suspected age-related pathology. Using a 4-parameter flowFISH assay to quantify telomere length in peripheral blood lymphocytes, we show in HIV-infected CMV-seropositive individuals (n=32) that CD57⁺CD8⁺ T cells responding to CMV had the shortest telomere lengths compared to CD57⁺CD8⁺, global CD8⁺ and CD8⁺ T cells responding to HIV (p < 0.001, 0.001, 0.04, respectively). CMV-seropositive HIV-infected study groups (n=97) show higher circulating pro-inflammatory cytokine levels than those not infected with CMV (n=19), further linking CMV immunity, immune senescence and inflammation. Our data support consideration that CMV infection associated expansion of CD8⁺ T cells compound the effects of natural aging on chronic inflammation.

Item Type: Thesis (Masters)
Item ID: 13191
Additional Information: Includes bibliographical references (pages 86-97).
Keywords: HIV, CMV, T cell senescence, Aging, Inflammation
Department(s): Medicine, Faculty of
Date: May 2018
Date Type: Submission
Library of Congress Subject Heading: Cytomegalovirus infections; T cells; HIV infections--Complications
Medical Subject Heading: Cytomegalovirus Infections; CD8-Positive T-Lymphocytes; HIV Infections--complications

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