title: Immune Activation and HIV-Specific CD8(+) T Cells in Cerebrospinal Fluid of HIV Controllers and Noncontrollers.
abstract: The central nervous system (CNS) is an important target of HIV, and cerebrospinal fluid (CSF) can provide a window into host-virus interactions within the CNS. The goal of this study was to determine whether HIV-specific CD8(+) T cells are present in CSF of HIV controllers (HC), who maintain low to undetectable plasma viremia without antiretroviral therapy (ART). CSF and blood were sampled from 11 HC, defined based on plasma viral load (VL) consistently below 2,000 copies/ml without ART. These included nine elite controllers (EC, plasma VL <40 copies/ml) and two viremic controllers (VC, VL 40-2,000 copies/ml). All controllers had CSF VL <40 copies/ml. Three comparison groups were also sampled: six HIV noncontrollers (NC, VL >10,000 copies/ml, no ART); seven individuals with viremia suppressed due to ART (Tx, VL <40 copies/ml); and nine HIV-negative controls. CD4(+) and CD8(+) T cells in CSF and blood were analyzed by flow cytometry to assess expression of CCR5, activation markers CD38 and HLA-DR, and memory/effector markers CD45RA and CCR7. HIV-specific CD8(+) T cells were quantified by major histocompatibility complex class I multimer staining. HIV-specific CD8(+) T cells were detected ex vivo at similar frequencies in CSF of HC and noncontrollers; the highest frequencies were in individuals with CD4 counts below 500 cells/μl. The majority of HIV-specific CD8(+) T cells in CSF were effector memory cells expressing CCR5. Detection of these cells in CSF suggests active surveillance of the CNS compartment by HIV-specific T cells, including in individuals with long-term control of HIV infection in the absence of therapy.
authors.affiliation: 1 Department of Medical Microbiology and Immunology, University of California , Davis, Davis, California.
authors.forename: Anupama
authors.initials: A
authors.lastname: Ganesh
authors.affiliation: 1 Department of Medical Microbiology and Immunology, University of California , Davis, Davis, California.
authors.forename: Donna
authors.initials: D
authors.lastname: Lemongello
authors.affiliation: 2 Department of Neurology, San Francisco General Hospital, University of California , San Francisco, San Francisco, California.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Lee
authors.affiliation: 2 Department of Neurology, San Francisco General Hospital, University of California , San Francisco, San Francisco, California.
authors.forename: Julia
authors.initials: J
authors.lastname: Peterson
authors.affiliation: 1 Department of Medical Microbiology and Immunology, University of California , Davis, Davis, California.
authors.forename: Bridget E
authors.initials: BE
authors.lastname: McLaughlin
authors.affiliation: 1 Department of Medical Microbiology and Immunology, University of California , Davis, Davis, California.
authors.forename: April L
authors.initials: AL
authors.lastname: Ferre
authors.affiliation: 3 Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford , Oxford, United Kingdom .
authors.forename: Geraldine M
authors.initials: GM
authors.lastname: Gillespie
authors.affiliation: 4 Division of Biological Chemistry, Innsbruck Medical University , Innsbruck, Austria .
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
authors.affiliation: 5 Department of Medicine, San Francisco General Hospital, University of California , San Francisco, San Francisco, California.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.affiliation: 5 Department of Medicine, San Francisco General Hospital, University of California , San Francisco, San Francisco, California.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hunt
authors.affiliation: 2 Department of Neurology, San Francisco General Hospital, University of California , San Francisco, San Francisco, California.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Price
authors.affiliation: 2 Department of Neurology, San Francisco General Hospital, University of California , San Francisco, San Francisco, California.
authors.forename: Serena S
authors.initials: SS
authors.lastname: Spudich
authors.affiliation: 1 Department of Medical Microbiology and Immunology, University of California , Davis, Davis, California.
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Shacklett
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics / Q000276:immunology; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D060467:Disease Resistance / Q000235:genetics*; D015870:Gene Expression; D015658:HIV Infections / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D054884:Host-Pathogen Interactions; D006801:Humans; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D012367:RNA, Viral / Q000276:immunology*; D019713:Receptors, CCR5 / Q000235:genetics / Q000276:immunology; D054400:Receptors, CCR7 / Q000235:genetics / Q000276:immunology; D019562:Viral Load / Q000187:drug effects / Q000235:genetics; D014766:Viremia / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000276:immunology* / Q000821:virology
chemical_list: D019380:Anti-HIV Agents; C584933:CCR5 protein, human; C515370:CCR7 protein, human; D006684:HLA-DR Antigens; D012367:RNA, Viral; D019713:Receptors, CCR5; D054400:Receptors, CCR7; D017493:Leukocyte Common Antigens; D051997:ADP-ribosyl Cyclase 1