Acute Conditioning of Antigen-Expanded CD8+ T Cells via the GSK3β-mTORC Axis Differentially Dictates Their Immediate and Distal Responses after Antigen Rechallenge
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Acute Starvation of IL-2 Diminishes the Robustness of the Immediate Response of Antigen-Expanded CD8+ T Cells after Rechallenge with Antigen
2.2. Acute Starvation of IL-2 before Antigen Rechallenge Promotes Re-Expansion of CD8+ T Cells with Enhanced Production of TNFα after Antigen Stimulation
2.3. Tim-3 Is a Reversible Marker of the Acute Impact of IL-2, IL-7, and IL-15 in Antigen-Expanded CD8+ T Cells
2.4. Acute Conditioning of Antigen-Expanded CD8+ T Cells with the GSK-3β Inhibitor, TWS119, Prior to Antigen Rechallenge Decreases IL-2-Mediated Tim-3 Expression and the Robustness of Their Immediate Response to Antigen Rechallenge
2.5. Acute Conditioning of Antigen-Expanded CD8+ T Cells with the GSK-3β Inhibitor TWS119 Prior to Antigen Rechallenge Promotes Re-Expansion of CD8+ T Cells with Enhanced Production of TNFα after Antigen Stimulation
2.6. Acute Conditioning of Expanded CD8+ T Cells with Rapamycin, but Not with Torin1, Prior to Antigen Rechallenge Promotes Re-Expansion of CD8+ T Cells with Enhanced Production of TNFα and IFNγ after Antigen Stimulation
3. Discussion
4. Materials and Methods
4.1. Specimens
4.2. DC Preparation
4.3. Enrichment and Expansion of Antigen-Specific CD8+ T Cells
4.4. Tim-3 Kinetics, Reversion Analysis, and Annexin V Assay
4.5. Cell Stimulation, Intracellular Cytokine Staining, and Cytokine Release
4.6. β-Catenin Translocation Analysis and Phospho Flow
4.7. Flow Cytometry Cytotoxic Assay
4.8. Antigen Rechallenge and Re-Expansion of CD8+ T Cells
4.9. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Taborska, P.; Stakheev, D.; Svobodova, H.; Strizova, Z.; Bartunkova, J.; Smrz, D. Acute Conditioning of Antigen-Expanded CD8+ T Cells via the GSK3β-mTORC Axis Differentially Dictates Their Immediate and Distal Responses after Antigen Rechallenge. Cancers 2020, 12, 3766. https://doi.org/10.3390/cancers12123766
Taborska P, Stakheev D, Svobodova H, Strizova Z, Bartunkova J, Smrz D. Acute Conditioning of Antigen-Expanded CD8+ T Cells via the GSK3β-mTORC Axis Differentially Dictates Their Immediate and Distal Responses after Antigen Rechallenge. Cancers. 2020; 12(12):3766. https://doi.org/10.3390/cancers12123766
Chicago/Turabian StyleTaborska, Pavla, Dmitry Stakheev, Hana Svobodova, Zuzana Strizova, Jirina Bartunkova, and Daniel Smrz. 2020. "Acute Conditioning of Antigen-Expanded CD8+ T Cells via the GSK3β-mTORC Axis Differentially Dictates Their Immediate and Distal Responses after Antigen Rechallenge" Cancers 12, no. 12: 3766. https://doi.org/10.3390/cancers12123766