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Series GSE24081 Query DataSets for GSE24081
Status Public on Oct 03, 2010
Title Comparison of gene expression profiles of HIV-specific CD8 T cells from controllers and progressors
Organism Homo sapiens
Experiment type Expression profiling by array
Summary CD8+ T cells in chronic viral infections like HIV develop functional defects such as loss of IL-2 secretion and decreased proliferative potential that are collectively termed exhaustion1. Exhausted T cells express increased levels of multiple inhibitory receptors, such as Programmed Death 1 (PD-1). PD-1 inhibition contributes to impaired virus-specific T cell function in chronic infection because antibody-mediated blockade of its ligand, Programmed Death Ligand 1 (PD-L1) is sufficient to improve T cell function and reduce viral replication in animal models. Reversing PD-1 inhibition is therefore an attractive therapeutic target, but the cellular mechanisms by which PD-1 ligation results in T cell inhibition are not fully understood. PD-1 is thought to limit T cell activation by attenuating T cell receptor (TCR) signaling. It is not known whether PD-1 ligation also acts by upregulating genes in exhausted T cells that impair their function. Here, we analyzed gene-expression profiles from HIV-specific CD8+ T cells in patients with HIV and show that PD-1 coordinately upregulates a program of genes in exhausted CD8+ T cells from humans and mice. This program includes upregulation of basic leucine transcription factor, ATF-like (BATF), a transcription factor in the AP-1 family. Enforced expression of BATF was sufficient to impair T cell proliferation and cytokine secretion, while BATF knockdown reduced PD-1 inhibition. Silencing BATF in CD4+ and CD8+ T cells from chronic viremic patients rescued HIV-specific T cell function. Thus inhibitory receptors can cause T cell exhaustion by upregulating genes – such as BATF – that inhibit T cell function.
 
Overall design We sorted HIV-specific CD8+ T cells from 18 progressors and 24 controllers, cohorts with a two-log difference in mean viral load
 
Contributor(s) Haining WN, Nilsson B
Citation(s) 20890291
Submission date Sep 10, 2010
Last update date Jan 17, 2017
Contact name W. Nicholas Haining
Organization name Dana-Farber Cancer Institute
Department Pediatric Oncology
Lab Haining lab
Street address 44 Binney Street
City Boston
State/province MA
ZIP/Postal code 02115
Country USA
 
Platforms (1)
GPL3921 [HT_HG-U133A] Affymetrix HT Human Genome U133A Array
Samples (42)
GSM592950 HIV-specific CD8 T cells_Controller_940546
GSM592951 HIV-specific CD8 T cells_Controller_553064
GSM592952 HIV-specific CD8 T cells_Controller_632343
This SubSeries is part of SuperSeries:
GSE24082 Comparison of gene expression profiles of HIV-specific CD8 T cells from controllers and progressors and Jurkat cells with or without PD-1 ligation
Relations
BioProject PRJNA133651

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE24081_RAW.tar 99.9 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
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