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| Status |
Public on Mar 18, 2023 |
| Title |
Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Chronic viral infections are characterized by a state of CD8 T cell dysfunction termed exhaustion. A better understanding of the mechanisms that regulate CD8 T cell responses during chronic infection is required to improve immunotherapies that restore function in exhausted CD8 T cells. Here we identify a novel population of virus-specific CD8 T cells with a T follicular helper (Tfh)-like signature in mice chronically infected with lymphocytic choriomeningitis virus (LCMV). These Tfh-like CD8 T cells expressed the programmed cell death-1 (PD-1) inhibitory receptor but at the same time also expressed co-stimulatory molecules and had a gene signature that was related to CD8 T cell memory precursor cells and hematopoietic stem cells (HSC). These Tfh-like CD8 T cells acted as stem cells during chronic infection undergoing self-renewal and also differentiating into the terminally exhausted CD8 T cells that were present in both lymphoid and non-lymphoid tissues. The Tfh-like CD8 T cells were found only in lymphoid tissues and resided predominantly in the T cell zones along with naïve CD8 T cells. Interestingly, the proliferative burst after PD-1 blockade came almost exclusively from this Tfh-like CD8 T cell subset. Importantly, the transcription factor TCF1 played a cell intrinsic and essential role in the generation of Tfh-like CD8 T cells. Taken together, our study identifies Tfh-like CD8 T cells as the critical subset for maintaining the pool of virus-specific CD8 T cells during chronic infection and as the cells that proliferate after PD-1 blockade. These findings provide a better understanding of T cell exhaustion and have implications towards optimizing PD-1 directed immunotherapy.
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| Overall design |
12 samples isolated from CD8 T-cells in naïve mice (5 naive) and B16F10-GP bearing mice (3 PD-1+ Tim-3-, 4 PD-1+ Tim-3+) cells were analyzed
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| Contributor(s) |
Im S, Ahmed R |
| Citation(s) |
37782797 |
| Submission date |
Mar 15, 2023 |
| Last update date |
Feb 07, 2024 |
| Contact name |
Se Jin Im |
| E-mail(s) |
sejinim@skku.edu
|
| Organization name |
Sungkyunkwan University School of Medicine
|
| Department |
Department of Immunology
|
| Lab |
Infection and Tumor Immunology
|
| Street address |
2066, Seobu-ro, Jangan-gu
|
| City |
Suwon-si |
| State/province |
Gyeonggi-do |
| ZIP/Postal code |
16419 |
| Country |
South Korea |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA944969 |
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