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| Status |
Public on Jul 01, 2023 |
| Title |
Strength of CD28 costimulation directs self-renewal or differentiation of TCF-1+ PD-1+ CD8 T cells through metabolic regulation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
During persistent antigen stimulation, such as in chronic infections and cancer, T cells differentiate into a hypofunctional exhausted state to survive. Exhausted PD-1+ CD8 T cell responses are sustained by TCF-1+ precursors (Tpex) that self-renew or differentiate into exhausted T cells (Tex) that retain some effector function. Tpex have high expression of the costimulatory molecule CD28 and are the cells that respond to PD-1 targeted immunotherapy. Here, we demonstrate that abrogation of CD28 signaling impairs maintenance of anti-viral T cell responses during chronic infection. Low-level CD28 signaling was required to preserve mitochondrial fitness and self-renewal of Tpex, whereas stronger CD28 signaling enhanced glycolysis and promoted Tpex differentiation. Our findings show that CD28 signaling is essential for long-term maintenance of antigen-specific T cells during chronic stimulation, and suggest that the activation status of antigen presenting cells determines Tpex differentiation into more functional effector-like Tex cells.
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| Overall design |
Gene expression analysis of bulk sorted Tpex (CD73+) or Tex (Tim3+) P14 CD28flox CREert2+ (CD28neg) or creERT2neg (CD28+) from mice chronically infected with LCMV cl13 and 2 weeks post tamoxifen treatment to understand the molecular impact of CD28 loss in maintenance and differentiation of virus-specific T cells.
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| Contributor(s) |
Humblin E, Filipescu D, Kamphorst A |
| Citation(s) |
37624910 |
| |
| Submission date |
Apr 08, 2022 |
| Last update date |
Oct 02, 2023 |
| Contact name |
Dan Filipescu |
| E-mail(s) |
dan.filipescu@mssm.edu
|
| Phone |
2128249265
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| Organization name |
Icahn School of Medicine at Mount Sinai
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| Department |
Oncological Sciences
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| Lab |
Emily Bernstein
|
| Street address |
1470 Madison Ave
|
| City |
New York |
| State/province |
New York |
| ZIP/Postal code |
10029 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA824842 |
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