Chronic CD4+ T cell Activation & Depletion in HIV-1 Infection: Type I Interferon-Mediated Disruption of T Cell Dynamic - GSE9927
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.
--
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.
--
--
--
--
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 |
File |
---|
All fields are editable except the "Sample ID" column. To edit a cell, click within the cell. To edit a "date" cell, click on the calendar icon. To cancel an edit, press the ESC key.
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 |
Name | ||
---|---|---|
All Samples | Default | View |
In order to make new Group Sets or change settings, please log in. |
Group Set | |
---|---|
All Samples |