Abstract
Direct and indirect cytopathic mechanisms have been proposed to account for the loss of CD4+ T cells after infection with human immunodeficiency virus type 1 (HIV-1). We report here that HIV-1 infection of the human thymus in vivo results in thymocyte depletion by at least two different mechanisms. Thymocytes within multiple stages of differentiation are induced to die of apoptosis; most of these cells are uninfected. Additionally, thymopoiesis is interrupted by direct infection and destruction of intrathymic CD3-CD4+CD8- progenitor cells. These mechanisms are differentially induced by distinct isolates of HIV-1.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis
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CD3 Complex / analysis
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CD4 Antigens / analysis
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CD4-Positive T-Lymphocytes*
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CD8 Antigens / analysis
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Chimera
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Cytopathogenic Effect, Viral*
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DNA Nucleotidylexotransferase / analysis
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HIV-1 / classification
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HIV-1 / isolation & purification
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HIV-1 / physiology*
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Hematopoietic Stem Cells / pathology
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Hematopoietic Stem Cells / virology*
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Humans
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Immunomagnetic Separation
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Immunophenotyping
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Mice
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Mice, Inbred BALB C
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Mice, SCID
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Polymerase Chain Reaction
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Proviruses / isolation & purification
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T-Lymphocyte Subsets / pathology
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T-Lymphocyte Subsets / virology*
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Thymus Gland / pathology
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Thymus Gland / virology*
Substances
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CD3 Complex
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CD4 Antigens
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CD8 Antigens
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DNA Nucleotidylexotransferase