title: Enhancement of human immunodeficiency virus (HIV)-specific CD8+ T cells in cerebrospinal fluid compared to those in blood among antiretroviral therapy-naive HIV-positive subjects.
abstract: During untreated human immunodeficiency virus type 1 (HIV-1) infection, virus-specific CD8(+) T cells partially control HIV replication in peripheral lymphoid tissues, but host mechanisms of HIV control in the central nervous system (CNS) are incompletely understood. We characterized HIV-specific CD8(+) T cells in cerebrospinal fluid (CSF) and peripheral blood among seven HIV-positive antiretroviral therapy-naïve subjects. All had grossly normal brain magnetic resonance imaging and spectroscopy and normal neuropsychometric testing. Frequencies of epitope-specific CD8(+) T cells by direct tetramer staining were on average 2.4-fold higher in CSF than in blood (P = 0.0004), while HIV RNA concentrations were lower. Cells from CSF were readily expanded ex vivo and responded to a broader range of HIV-specific human leukocyte antigen class I restricted optimal peptides than did expanded cells from blood. HIV-specific CD8(+) T cells, in contrast to total CD8(+) T cells, in CSF and blood were at comparable maturation states, as assessed by CD45RO and CCR7 staining. The strong relationship between higher T-cell frequencies and lower levels of viral antigen in CSF could be the result of increased migration to and/or preferential expansion of HIV-specific T cells within the CNS. This suggests an important role for HIV-specific CD8(+) T cells in control of intrathecal viral replication.
authors: Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center, MCN A2200, Nashville, TN 37232. spyros.a.kalams@vanderbilt.edu.
authors: Shanmugalakshmi
authors: S
authors: Sadagopal
authors: Shelly L
authors: SL
authors: Lorey
authors: Louise
authors: L
authors: Barnett
authors: Rebecca
authors: R
authors: Basham
authors: Laurie
authors: L
authors: Lebo
authors: Husamettin
authors: H
authors: Erdem
authors: Kirsten
authors: K
authors: Haman
authors: Malcolm
authors: M
authors: Avison
authors: Kevin
authors: K
authors: Waddell
authors: David W
authors: DW
authors: Haas
authors: Spyros A
authors: SA
authors: Kalams
mesh_terms: D000328:Adult; D001769:Blood / Q000276:immunology* / Q000821:virology; D001921:Brain / Q000000981:diagnostic imaging / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D049109:Cell Proliferation; D002555:Cerebrospinal Fluid / Q000276:immunology* / Q000821:virology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000032:analysis; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid; D011859:Radiography; D054400:Receptors, CCR7 / Q000032:analysis; D019562:Viral Load
chemical_list: C515370:CCR7 protein, human; D012367:RNA, Viral; D054400:Receptors, CCR7; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens