title: Inflammatory Function of CX3CR1+ CD8+ T Cells in Treated HIV Infection Is Modulated by Platelet Interactions.
abstract: Increases in inflammation, coagulation, and CD8+T-cell numbers are associated with an elevated cardiovascular disease (CVD) risk in human immunodeficiency virus (HIV)-infected antiretroviral therapy (ART) recipients. Circulating memory CD8+T cells that express the vascular endothelium-homing receptor CX3CR1 (fractalkine receptor) are enriched in HIV-infected ART recipients. Thrombin-activated receptor (PAR-1) expression is increased in HIV-infected ART recipients and is particularly elevated on CX3CR1+CD8+T cells, suggesting that these cells could interact with coagulation elements. Indeed, thrombin directly enhanced T-cell receptor-mediated interferon γ production by purified CD8+T cells but was attenuated by thrombin-induced release of transforming growth factor β by platelets. We have therefore identified a population of circulating memory CD8+T cells in HIV infection that may home to endothelium, can be activated by clot-forming elements, and are susceptible to platelet-mediated regulation. Complex interactions between inflammatory elements and coagulation at endothelial surfaces may play an important role in CVD risk in HIV-infected ART recipients.
authors.affiliation: Center for AIDS Research, Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University/University Hospitals Cleveland Medical Center, Ohio.|National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Mudd
authors.affiliation: Center for AIDS Research, Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University/University Hospitals Cleveland Medical Center, Ohio.
authors.forename: Soumya
authors.initials: S
authors.lastname: Panigrahi
authors.affiliation: Center for AIDS Research, Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University/University Hospitals Cleveland Medical Center, Ohio.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kyi
authors.affiliation: Center for AIDS Research, Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University/University Hospitals Cleveland Medical Center, Ohio.
authors.forename: So Hee
authors.initials: SH
authors.lastname: Moon
authors.affiliation: Center for AIDS Research, Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University/University Hospitals Cleveland Medical Center, Ohio.|National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Maura M
authors.initials: MM
authors.lastname: Manion
authors.affiliation: Center for AIDS Research, Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University/University Hospitals Cleveland Medical Center, Ohio.
authors.forename: Souheil-Antoine
authors.initials: SA
authors.lastname: Younes
authors.affiliation: Center for AIDS Research, Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University/University Hospitals Cleveland Medical Center, Ohio.
authors.forename: Scott F
authors.initials: SF
authors.lastname: Sieg
authors.affiliation: Division of Medical Laboratory Sciences, School of Health and Rehabilitation Sciences, Ohio State University, Columbus.
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Funderburg
authors.affiliation: Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Ohio.
authors.forename: David A
authors.initials: DA
authors.lastname: Zidar
authors.affiliation: Center for AIDS Research, Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University/University Hospitals Cleveland Medical Center, Ohio.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.affiliation: Center for AIDS Research, Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University/University Hospitals Cleveland Medical Center, Ohio.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Freeman
mesh_terms: D001792:Blood Platelets / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D000073883:CX3C Chemokine Receptor 1; D015658:HIV Infections / Q000276:immunology / Q000473:pathology*; D006801:Humans; D019707:Receptors, Chemokine / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D019707:Receptors, Chemokine; D016212:Transforming Growth Factor beta
keywords: CD8+ T-cell expansion; atherosclerosis; non–AIDS-related morbidities; platelets