Brain CD8+ and cytotoxic T lymphocytes are associated with, and may be specific for, human immunodeficiency virus type 1 encephalitis in patients with acquired immunodeficiency syndrome

Carol Petito, Jorge E. Torres-Muñoz, Fabiana Zielger, Micheline McCarthy

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

CD8+ T cells infiltrate brains with human immunodeficiency virus type-1 (HIV-1) encephalitis (HIVE) and related animal models; their perineuronal localization suggests cytotoxic T cell (CTL)-mediated neuronal killing. Because CTLs have not been identified in acquired immunodeficiency syndrome (AIDS) brains, the authors identified their cytotoxic granules in autopsy AIDS brains with HIVE and without HIVE (HIVnE) plus controls (7 to 13 cases/group) and determined gene expression profiles of CTL-associated genes in a separate series of cases. CD3+ and CD8+ T cells were significantly increased (P < .01) in perivascular spaces and inflammatory nodules in HIVE but were rare or absent in brain parenchyma in HIVnE and control brains. Eight HIVE brains contained granzyme B+ T cells and five contained perforin+ T cells. Their T-cell origin was confirmed by colocalization of CD8 and granzyme B in the same cell and the absence of CD56+ natural killer cells. The CTLs directly contacted with neurons, as the authors showed previously for CD3+ and CD8+ T cells. CTLs were rare or absent in HIV nonencephalitis (HIVnE) and controls. Granzyme B and H precursor gene expression was up-regulated and interleukin (IL)-12A precursor, a maturation factor for natural killer cells and CTLs, was down-regulated in HIVE versus HIVnE brain. This study demonstrates, for the first time, CTLs in HIVE and shows that parenchymal T cells and CTLs are sensitive biomarkers for HIVE. Consequently, CD8+ T cells and CTLs could mediate brain injury in HIVE and may represent an important biomarker for productive brain infection by HIV-1.

Original languageEnglish
Pages (from-to)272-283
Number of pages12
JournalJournal of NeuroVirology
Volume12
Issue number4
DOIs
StatePublished - Aug 1 2006

Fingerprint

Cytotoxic T-Lymphocytes
Encephalitis
HIV-1
Acquired Immunodeficiency Syndrome
T-Lymphocytes
Brain
Granzymes
HIV
Natural Killer Cells
Interleukin-12 Subunit p35
Biomarkers
Perforin
Transcriptome
Brain Injuries
Autopsy
Animal Models
Gene Expression
Neurons

Keywords

  • CNS
  • HIV-1-associated dementia
  • Microarrays
  • Neurons
  • Perforin/granzyme B
  • Virus

ASJC Scopus subject areas

  • Virology
  • Clinical Neurology

Cite this

Brain CD8+ and cytotoxic T lymphocytes are associated with, and may be specific for, human immunodeficiency virus type 1 encephalitis in patients with acquired immunodeficiency syndrome. / Petito, Carol; Torres-Muñoz, Jorge E.; Zielger, Fabiana; McCarthy, Micheline.

In: Journal of NeuroVirology, Vol. 12, No. 4, 01.08.2006, p. 272-283.

Research output: Contribution to journalArticle

@article{60ad671cda794913bb8c7ade8408ef0b,
title = "Brain CD8+ and cytotoxic T lymphocytes are associated with, and may be specific for, human immunodeficiency virus type 1 encephalitis in patients with acquired immunodeficiency syndrome",
abstract = "CD8+ T cells infiltrate brains with human immunodeficiency virus type-1 (HIV-1) encephalitis (HIVE) and related animal models; their perineuronal localization suggests cytotoxic T cell (CTL)-mediated neuronal killing. Because CTLs have not been identified in acquired immunodeficiency syndrome (AIDS) brains, the authors identified their cytotoxic granules in autopsy AIDS brains with HIVE and without HIVE (HIVnE) plus controls (7 to 13 cases/group) and determined gene expression profiles of CTL-associated genes in a separate series of cases. CD3+ and CD8+ T cells were significantly increased (P < .01) in perivascular spaces and inflammatory nodules in HIVE but were rare or absent in brain parenchyma in HIVnE and control brains. Eight HIVE brains contained granzyme B+ T cells and five contained perforin+ T cells. Their T-cell origin was confirmed by colocalization of CD8 and granzyme B in the same cell and the absence of CD56+ natural killer cells. The CTLs directly contacted with neurons, as the authors showed previously for CD3+ and CD8+ T cells. CTLs were rare or absent in HIV nonencephalitis (HIVnE) and controls. Granzyme B and H precursor gene expression was up-regulated and interleukin (IL)-12A precursor, a maturation factor for natural killer cells and CTLs, was down-regulated in HIVE versus HIVnE brain. This study demonstrates, for the first time, CTLs in HIVE and shows that parenchymal T cells and CTLs are sensitive biomarkers for HIVE. Consequently, CD8+ T cells and CTLs could mediate brain injury in HIVE and may represent an important biomarker for productive brain infection by HIV-1.",
keywords = "CNS, HIV-1-associated dementia, Microarrays, Neurons, Perforin/granzyme B, Virus",
author = "Carol Petito and Torres-Mu{\~n}oz, {Jorge E.} and Fabiana Zielger and Micheline McCarthy",
year = "2006",
month = "8",
day = "1",
doi = "10.1080/13550280600879204",
language = "English",
volume = "12",
pages = "272--283",
journal = "Journal of NeuroVirology",
issn = "1355-0284",
publisher = "Springer New York",
number = "4",

}

TY - JOUR

T1 - Brain CD8+ and cytotoxic T lymphocytes are associated with, and may be specific for, human immunodeficiency virus type 1 encephalitis in patients with acquired immunodeficiency syndrome

AU - Petito, Carol

AU - Torres-Muñoz, Jorge E.

AU - Zielger, Fabiana

AU - McCarthy, Micheline

PY - 2006/8/1

Y1 - 2006/8/1

N2 - CD8+ T cells infiltrate brains with human immunodeficiency virus type-1 (HIV-1) encephalitis (HIVE) and related animal models; their perineuronal localization suggests cytotoxic T cell (CTL)-mediated neuronal killing. Because CTLs have not been identified in acquired immunodeficiency syndrome (AIDS) brains, the authors identified their cytotoxic granules in autopsy AIDS brains with HIVE and without HIVE (HIVnE) plus controls (7 to 13 cases/group) and determined gene expression profiles of CTL-associated genes in a separate series of cases. CD3+ and CD8+ T cells were significantly increased (P < .01) in perivascular spaces and inflammatory nodules in HIVE but were rare or absent in brain parenchyma in HIVnE and control brains. Eight HIVE brains contained granzyme B+ T cells and five contained perforin+ T cells. Their T-cell origin was confirmed by colocalization of CD8 and granzyme B in the same cell and the absence of CD56+ natural killer cells. The CTLs directly contacted with neurons, as the authors showed previously for CD3+ and CD8+ T cells. CTLs were rare or absent in HIV nonencephalitis (HIVnE) and controls. Granzyme B and H precursor gene expression was up-regulated and interleukin (IL)-12A precursor, a maturation factor for natural killer cells and CTLs, was down-regulated in HIVE versus HIVnE brain. This study demonstrates, for the first time, CTLs in HIVE and shows that parenchymal T cells and CTLs are sensitive biomarkers for HIVE. Consequently, CD8+ T cells and CTLs could mediate brain injury in HIVE and may represent an important biomarker for productive brain infection by HIV-1.

AB - CD8+ T cells infiltrate brains with human immunodeficiency virus type-1 (HIV-1) encephalitis (HIVE) and related animal models; their perineuronal localization suggests cytotoxic T cell (CTL)-mediated neuronal killing. Because CTLs have not been identified in acquired immunodeficiency syndrome (AIDS) brains, the authors identified their cytotoxic granules in autopsy AIDS brains with HIVE and without HIVE (HIVnE) plus controls (7 to 13 cases/group) and determined gene expression profiles of CTL-associated genes in a separate series of cases. CD3+ and CD8+ T cells were significantly increased (P < .01) in perivascular spaces and inflammatory nodules in HIVE but were rare or absent in brain parenchyma in HIVnE and control brains. Eight HIVE brains contained granzyme B+ T cells and five contained perforin+ T cells. Their T-cell origin was confirmed by colocalization of CD8 and granzyme B in the same cell and the absence of CD56+ natural killer cells. The CTLs directly contacted with neurons, as the authors showed previously for CD3+ and CD8+ T cells. CTLs were rare or absent in HIV nonencephalitis (HIVnE) and controls. Granzyme B and H precursor gene expression was up-regulated and interleukin (IL)-12A precursor, a maturation factor for natural killer cells and CTLs, was down-regulated in HIVE versus HIVnE brain. This study demonstrates, for the first time, CTLs in HIVE and shows that parenchymal T cells and CTLs are sensitive biomarkers for HIVE. Consequently, CD8+ T cells and CTLs could mediate brain injury in HIVE and may represent an important biomarker for productive brain infection by HIV-1.

KW - CNS

KW - HIV-1-associated dementia

KW - Microarrays

KW - Neurons

KW - Perforin/granzyme B

KW - Virus

UR - http://www.scopus.com/inward/record.url?scp=33748636954&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748636954&partnerID=8YFLogxK

U2 - 10.1080/13550280600879204

DO - 10.1080/13550280600879204

M3 - Article

C2 - 16966218

AN - SCOPUS:33748636954

VL - 12

SP - 272

EP - 283

JO - Journal of NeuroVirology

JF - Journal of NeuroVirology

SN - 1355-0284

IS - 4

ER -