Immune Activation and HIV-Specific CD8(+) T Cells in Cerebrospinal Fluid of HIV Controllers and Noncontrollers. 2016

Anupama Ganesh, and Donna Lemongello, and Evelyn Lee, and Julia Peterson, and Bridget E McLaughlin, and April L Ferre, and Geraldine M Gillespie, and Dietmar Fuchs, and Steven G Deeks, and Peter W Hunt, and Richard W Price, and Serena S Spudich, and Barbara L Shacklett
1 Department of Medical Microbiology and Immunology, University of California , Davis, Davis, California.

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.

UI MeSH Term Description Entries
D008213 Lymphocyte Activation Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION. Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D006684 HLA-DR Antigens A subclass of HLA-D antigens that consist of alpha and beta chains. The inheritance of HLA-DR antigens differs from that of the HLA-DQ ANTIGENS and HLA-DP ANTIGENS. HLA-DR,Antigens, HLA-DR,HLA DR Antigens
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012367 RNA, Viral Ribonucleic acid that makes up the genetic material of viruses. Viral RNA
D014766 Viremia The presence of viruses in the blood. Viremias
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D015658 HIV Infections Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS). HTLV-III Infections,HTLV-III-LAV Infections,T-Lymphotropic Virus Type III Infections, Human,HIV Coinfection,Coinfection, HIV,Coinfections, HIV,HIV Coinfections,HIV Infection,HTLV III Infections,HTLV III LAV Infections,HTLV-III Infection,HTLV-III-LAV Infection,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,T Lymphotropic Virus Type III Infections, Human
D015870 Gene Expression The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION. Expression, Gene,Expressions, Gene,Gene Expressions
D017493 Leukocyte Common Antigens High-molecular weight glycoproteins uniquely expressed on the surface of LEUKOCYTES and their hemopoietic progenitors. They contain two FIBRONECTIN TYPE III DOMAINS and possess cytoplasmic protein tyrosine phosphatase activity, which plays a role in intracellular signaling from the CELL SURFACE RECEPTORS. Leukocyte common antigens occur as multiple isoforms that result from alternative mRNA splicing and differential usage of three exons. Antigens, CD45,CD45 Antigens,CD45R Antigens,CD45RA Antigens,CD45RO Antigens,Protein Tyrosine Phosphatase, Receptor Type, C,2H4 Antigens,B220 Antigen,B220 Antigens,CD45 Antigen,CD45R0 Antigens,CD45RB Antigens,CD45RCAntigens,L-CA Antigens,Leukocyte Common Antigen,T200 Antigens,Antigen, B220,Antigen, CD45,Antigen, Leukocyte Common,Antigens, 2H4,Antigens, B220,Antigens, CD45R,Antigens, CD45R0,Antigens, CD45RA,Antigens, CD45RB,Antigens, CD45RO,Antigens, L-CA,Antigens, Leukocyte Common,Antigens, T200,L CA Antigens
D051997 ADP-ribosyl Cyclase 1 A bifunctional enzyme that catalyzes the synthesis and HYDROLYSIS of CYCLIC ADP-RIBOSE (cADPR) from NAD+ to ADP-RIBOSE. It is a cell surface molecule which is predominantly expressed on LYMPHOID CELLS and MYELOID CELLS. Antigens, CD38,CD38 Antigens,ADPR Cyclase CD38,ADPR Cyclase T10,Acute Lymphoblastic Leukemia Cells Antigen CD38,CD38 Antigen,Lymphocyte Differentiation Antigen CD38,NIM-R5 Antigen,T10 Antigen,1, ADP-ribosyl Cyclase,ADP ribosyl Cyclase 1,Antigen, T10,CD38, ADPR Cyclase,Cyclase 1, ADP-ribosyl,Cyclase CD38, ADPR,Cyclase T10, ADPR,NIM R5 Antigen

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