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.
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.
Sadagopal
Shanmugalakshmi
S
Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center, MCN A2200, Nashville, TN 37232. spyros.a.kalams@vanderbilt.edu.
Lorey
Shelly L
SL
Barnett
Louise
L
Basham
Rebecca
R
Lebo
Laurie
L
Erdem
Husamettin
H
Haman
Kirsten
K
Avison
Malcolm
M
Waddell
Kevin
K
Haas
David W
DW
Kalams
Spyros A
SA
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
C515370:CCR7 protein, human; D012367:RNA, Viral; D054400:Receptors, CCR7; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens