|
| Status |
Public on Sep 12, 2020 |
| Title |
An Atlas of Immune Cell Exhaustion in HIV-Infected Individuals Revealed by Single-Cell Transcriptomics |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
We investigated the effects of HIV infection on immune cell exhaustion at the transcriptomic level by analyzing single-cell RNA sequencing of peripheral blood mononuclear cells from four healthy subjects (37,847 cells) and six HIV-infected donors (28,610 cells). We identified nine immune cell clusters and eight T cell subclusters according to their unique gene expression programs; three of these (exhausted CD4+ and CD8+ T cells and interferon-responsive CD8+ T cells) were detected only in samples from HIV-infected donors. An inhibitory receptor KLRG1 was identified in the exhausted T cell populations and further characterized in HIV infected individuals. We identified a HIV-1 specific exhausted CD8+ T cell population expressing KLRG1, TIGIT, and T-betdimEomeshi markers. Ex-vivo antibody blockade of KLRG1 restored the function of HIV-specific exhausted CD8+ T cells demonstrating the contribution of KLRG1+ population to T cell exhaustion and providing an immunotherapy target to treat HIV chronic infection. Analysis of gene signatures also revealed impairment of B cell and NK cell function in HIV-infected donors. These data provide a comprehensive analysis of gene signatures associated with immune cell exhaustion during HIV infection, which could be useful in understanding exhaustion mechanisms and developing new cure therapies.
|
| |
|
| Overall design |
PBMCs from 6 HIV patients and 1 Healthy donor were subjected to scRNA seq.
|
| |
|
| Contributor(s) |
Wang S, Zhang Q, Hui H |
| Citation(s) |
32954948 |
| |
| Submission date |
Sep 11, 2020 |
| Last update date |
Nov 24, 2020 |
| Contact name |
Shaobo Wang |
| E-mail(s) |
shw329@health.ucsd.edu
|
| Phone |
4049446750
|
| Organization name |
University of California San Diego
|
| Street address |
9500 Gilman Dr., La Jolla, San Diego
|
| City |
SAN DIEGO |
| State/province |
California |
| ZIP/Postal code |
92093 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (7)
|
|
| Relations |
| BioProject |
PRJNA662927 |
| SRA |
SRP282057 |
Less...
More...