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Chronic CD4+ T cell Activation & Depletion in HIV-1 Infection: Type I Interferon-Mediated Disruption of T Cell Dynamic - GSE9927

Purpose

The mechanism of CD4(+) T cell depletion during chronic human immunodeficiency virus type 1 (HIV-1) infection remains unknown. Many studies suggest a significant role for chronic CD4(+) T cell activation. We assumed that the pathogenic process of excessive CD4(+) T cell activation would be reflected in the transcriptional profiles of activated CD4(+) T cells. Here we demonstrate that the transcriptional programs of in vivo activated CD4(+) T cells from untreated HIV(+) individuals are clearly different from those activated CD4(+) T cells from HIV(-) individuals. We observed a dramatic up-regulation of cell cycle-associated and interferon-stimulated transcripts in activated CD4(+) T cells of untreated HIV(+) individuals. Furthermore, we find an enrichment of proliferative and Type I interferon-responsive transcription factor binding sites in the promoters of genes that are differentially expressed in activated CD4(+) T cells of untreated HIV(+) individuals compared to HIV(-) individuals. We confirm these findings by examination of in vivo activated CD4(+) T cells. Taken together, these results suggest that activated CD4(+) T cells from untreated HIV(+) individuals are in a hyper-proliferative state that is modulated by Type I interferons. From these results, we propose a new model for CD4(+) T cell depletion during chronic HIV-1 infection.

Hypothesis

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Experimental Design

This experiment compares the expression of CD4+ T-cells obtained from 11 HIV+ individuals with that from comparable 9 HIV- control individuals. Each individual's cells were analyzed on separate single-color chips, and the average values of both biological replicate groups were analyzed for statistical significance.

The biological significance of up- and down-regulated probesets/genes was analyzed using the Gene Ontology annotation dataset.

Experimental Variables

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Controls

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Methods

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Additional Information

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Microarray
Affymetrix HG-U133_Plus_2
20 Samples Loaded: 20
Human (Homo sapiens)
CD4 T cells
HIV
Sample Set Spreadsheet
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Samples Preview
Sample ID !Sample_title CD4+ T-cells from HIV+ donor CD4+ T-cells from normal HIV- donor
GSM251101 Normal Control C-10a True
GSM251105 Normal Control C-1a True
GSM251110 Normal Control C-2a True
GSM251111 Normal Control C-3a True
GSM251114 Normal Control C-4a True
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Sample ID !Sample Title CD4+ T-cells from HIV+ donor CD4+ T-cells from normal HIV- donor
GSM251101
Normal Control C-10a
 
True
GSM251105
Normal Control C-1a
 
True
GSM251110
Normal Control C-2a
 
True
GSM251111
Normal Control C-3a
 
True
GSM251114
Normal Control C-4a
 
True
GSM251126
Normal Control C-5a
 
True
GSM251129
Normal Control C-6a
 
True
GSM251192
Normal Control C-7a
 
True
GSM251194
Normal Control C-8a
 
True
GSM251195
HIV+ Individual HIV-10a
True
 
GSM251196
HIV+ Individual HIV-11a
True
 
GSM251197
HIV+ Individual HIV-1a
True
 
GSM251198
HIV+ Individual HIV-2a
True
 
GSM251199
HIV+ Individual HIV-3a
True
 
GSM251200
HIV+ Individual HIV-4a
True
 
GSM251207
HIV+ Individual HIV-5a
True
 
GSM251208
HIV+ Individual HIV-6a
True
 
GSM251209
HIV+ Individual HIV-7a
True
 
GSM251210
HIV+ Individual HIV-8a
True
 
GSM251211
HIV+ Individual HIV-9a
True
 

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