Generation of cytotoxic T cells against virus-infected human brain macrophages in a murine model of HIV-1 encephalitis

Larisa Y. Poluektova, David H Munn, Yuri Persidsky, Howard E. Gendelman

Research output: Contribution to journalArticle

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Abstract

HIV-1 encephalitis (HIVE) and its associated dementia can occur in up to 20% of infected individuals, usually when productive viral replication in brain mononuclear phagocytes (macrophages and microglia) and depletion of CD4+ T lymphocytes are most significant. T cells control viral replication through much of HIV-1 disease, but how this occurs remains incompletely understood. With this in mind, we studied HIV-1-specific CTL responses in a nonobese diabetic (NOD)-SCID mouse model of HIVE. HIV-1-infected monocyte-derived macrophages (MDM) were injected into the basal ganglia after syngeneic immune reconstitution by HLA-A*0201-positive human PBL to generate a human PBL-NOD-SCID HIVE mouse. Engrafted T lymphocytes produced HIV-1gag- and HIV-1pol-specific CTL against virus-infected brain MDM within 7 days. This was demonstrated by tetramer staining of human PBL in mouse spleens and by IFN-γ ELISPOT. CD8, granzyme B, HLA-DR, and CD45R0 Ag-reactive T cells and CD79α-positive B cells migrated to and were in contact with human MDM in brain areas where infected macrophages were abundant. The numbers of productively infected MDM were markedly reduced (>85%) during 2 wk of observation. The human PBL-NOD-SCID HIVE mouse provides a new tool for studies of cellular immune responses against HIV-1-infected brain mononuclear phagocytes during natural disease and after vaccination.

Original languageEnglish (US)
Pages (from-to)3941-3949
Number of pages9
JournalJournal of Immunology
Volume168
Issue number8
DOIs
StatePublished - Apr 15 2002
Externally publishedYes

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Encephalitis
HIV-1
Macrophages
Viruses
T-Lymphocytes
Brain
Phagocytes
HIV
Enzyme-Linked Immunospot Assay
Granzymes
Inbred NOD Mouse
SCID Mice
Microglia
HLA-DR Antigens
Basal Ganglia
Cellular Immunity
Dementia
Vaccination
B-Lymphocytes
Spleen

ASJC Scopus subject areas

  • Immunology

Cite this

Generation of cytotoxic T cells against virus-infected human brain macrophages in a murine model of HIV-1 encephalitis. / Poluektova, Larisa Y.; Munn, David H; Persidsky, Yuri; Gendelman, Howard E.

In: Journal of Immunology, Vol. 168, No. 8, 15.04.2002, p. 3941-3949.

Research output: Contribution to journalArticle

Poluektova, Larisa Y. ; Munn, David H ; Persidsky, Yuri ; Gendelman, Howard E. / Generation of cytotoxic T cells against virus-infected human brain macrophages in a murine model of HIV-1 encephalitis. In: Journal of Immunology. 2002 ; Vol. 168, No. 8. pp. 3941-3949.
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