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| Status |
Public on Apr 01, 2019 |
| Title |
The role of IFN-I and IL-27 in the expansion of virus-specific CD8+ T cell subtypes during persistent infection |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Chronic infection and cancer are associated with suppressed T cell responses in the presence of activating antigen. Recent work identified memory-like CD8+ T cells termed follicular cytotoxic T cells (TFC) which sustain T cell responses during persistent infection and are essential for the T-cell proliferative burst following PD1 blockade. Approaches to expand these cells are sought. We show that blockade of interferon type 1 (IFN-I) receptor leads to TFC expansion in an IL-27-and STAT1-dependent manner. IFNAR1 blockade promoted accelerated cell division and retention of TCF1 in virus-specific CD8+ T cells. We found that CD8+ T cell-intrinsic IL-27 signaling safeguards the ability of TCF1-high cells to sustain proliferation and prevents premature cell cycle exit and programmed cell death. Transcriptome analysis revealed an IL-27-regulated gene module controlling survival of activated CD8+ T cells which is enhanced in IFNAR-attenuated conditions. We further demonstrated a cell-intrinsic requirement for the IL-27 target IRF1 in TFC expansion through promoting sustained division. These findings reveal that IL-27 opposes IFN-I to uncouple cell division from effector differentiation, and suggest IL-27 signaling could be exploited to augment self-renewing T cell populations in patients with chronic infections.
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| Overall design |
Cells were isolated from mouse spleens, sorted using flow cytometry and RNA isolated for sequencing. 3 replicates per biological group were used, each sample represents cells from an individual mouse.
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| Contributor(s) |
Zak J, Huang Z, Teijaro JR, Pratumchai I |
| Citation(s) |
31164392 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 AI118862 |
IL-27 elicited antibodies: A novel means to control persistent Arenavirus infection |
THE SCRIPPS RESEARCH INSTITUTE |
John Ross Teijaro |
| R01 AI123210 |
Novel Strategies for Controlling Persistent Viral Infection |
THE SCRIPPS RESEARCH INSTITUTE |
John Ross Teijaro |
| R21 AI143529 |
Novel Regulators of B Cell Tolerance |
THE SCRIPPS RESEARCH INSTITUTE |
Changchun Xiao |
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| |
| Submission date |
Mar 28, 2017 |
| Last update date |
Jul 02, 2019 |
| Contact name |
John R Teijaro |
| E-mail(s) |
teijaro@scripps.edu
|
| Organization name |
The Scripps Research Institute
|
| Department |
Immunology and Microbial Science
|
| Street address |
10550 North Torrey Pines Rd
|
| City |
San Diego |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (47)
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| Relations |
| BioProject |
PRJNA380798 |
| SRA |
SRP102615 |
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