title: Immunosenescence of the CD8(+) T cell compartment is associated with HIV-infection, but only weakly reflects age-related processes of adipose tissue, metabolism, and muscle in antiretroviral therapy-treated HIV-infected patients and controls.
abstract: BACKGROUND
  Despite effective antiretroviral therapy (ART), HIV-infected patients exhibit systemic inflammation, early onset of age-related diseases, and features of immunosenescence. The role of inflammation in the development of age-related diseases is widely recognized. However, the role of immunosenescence is not well established. Studying immunosenescence in HIV-infection could give insight into its role in ageing processes. In this cross-sectional study, we aimed to investigate whether ART-treated HIV-infected patients exhibit immunosenescence; and whether immunosenescence is associated with age-related processes of inflammation, metabolism, adipose tissue, and muscle. T cell immunosenescence and exhaustion were assessed by flow cytometry analysis of CD8 (+) cells from 43 ART-treated HIV-infected patients (HIV(+)) and ten Controls using markers of differentiation: CD27/CD28; maturation: CD27/CD45RA; senescence: killer cell lectin-like receptor G1 (KLRG1); and exhaustion: programmed death-1 (PD-1). Relationships between CD8 (+) T cell immunosenescence, exhaustion, and age-related processes were assessed using linear regressions.
  
  
  RESULTS
  HIV-infection was strongly associated with more highly differentiated and mature CD8 (+) T cell phenotypes. PD-1 and KLRG1 expression did not differ between HIV(+) and Controls, but depended on differentiation and maturation stages of the cells. CD8 (+) T cell maturation was associated with age. KLRG1 expression was associated with age, metabolic syndrome, visceral adipose tissue, and high muscle mass. PD-1 expression was not associated with age-related parameters.
  
  
  CONCLUSIONS
  HIV-infection strongly affected CD8 (+) T cell differentiation and maturation, whereas age-related processes were only weakly associated with immune parameters. Our findings suggest that, in contrast to inflammation, immunosenescence appears to be highly dependent on HIV-infection and is only to a small extent associated with age-related parameters in well-treated HIV-infection.
authors.affiliation: Optimed, Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Kettegård Alle 30, DK-2650, Hvidovre, Denmark. juliette.tavenier@regionh.dk.
authors.forename: Juliette
authors.initials: J
authors.lastname: Tavenier
authors.affiliation: Optimed, Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Kettegård Alle 30, DK-2650, Hvidovre, Denmark. anne.langkilde@regionh.dk.
authors.forename: Anne
authors.initials: A
authors.lastname: Langkilde
authors.affiliation: Optimed, Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Kettegård Alle 30, DK-2650, Hvidovre, Denmark. thomas.huneck.haupt.01@regionh.dk.
authors.forename: Thomas Huneck
authors.initials: TH
authors.lastname: Haupt
authors.affiliation: Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital, Hvidovre, Kettegård Alle 30, DK-2650, Hvidovre, Denmark. jens.henrik.henriksen@regionh.dk.
authors.forename: Jens Henrik
authors.initials: JH
authors.lastname: Henriksen
authors.affiliation: Department of Radiology, Copenhagen University Hospital, Hvidovre, Kettegård Alle 30, DK-2650, Hvidovre, Denmark. frank.krieger.jensen@regionh.dk.
authors.forename: Frank Krieger
authors.initials: FK
authors.lastname: Jensen
authors.affiliation: Optimed, Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Kettegård Alle 30, DK-2650, Hvidovre, Denmark. janne.petersen.01@regionh.dk.|Section of Biostatistics, Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Øster Farimagsgade 5, 1014, Copenhagen K., Denmark. janne.petersen.01@regionh.dk.
authors.forename: Janne
authors.initials: J
authors.lastname: Petersen
authors.affiliation: Optimed, Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Kettegård Alle 30, DK-2650, Hvidovre, Denmark. ove.andersen@regionh.dk.|Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Kettegård Alle 30, DK-2650, Hvidovre, Denmark. ove.andersen@regionh.dk.
authors.forename: Ove
authors.initials: O
authors.lastname: Andersen
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000367:Age Factors; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers; D001823:Body Composition; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004734:Energy Metabolism; D005260:Female; D015870:Gene Expression; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D056747:Immunomodulation; D016130:Immunophenotyping; D000068884:Immunosenescence; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000378:metabolism*; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; C113413:KLRG1 protein, human; D037181:Lectins, C-Type; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic; D015534:Trans-Activators