|
| Status |
Public on Oct 03, 2010 |
| Title |
Comparison of gene expression profiles of Jurkat cells with or without PD-1 ligation |
| 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 |
PD-1 expressing Jurkat cells were cultured for 18 hours with beads coated with antibodies to CD3 and CD28, with our without an antibody to PD-1.
|
| |
|
| Contributor(s) |
Haining N, Nilsson B |
| Citation(s) |
20890291 |
| Submission date |
Sep 08, 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 (11)
|
|
| 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 |
PRJNA133219 |
Less...
More...