Conserved Region C Functions To Regulate PD-1 Expression and Subsequent CD8 T Cell Memory.
Alexander P R BallyYan TangJoshua T LeeBenjamin G BarwickRyan MartinezBrian D EvavoldJeremy M BossPublished in: Journal of immunology (Baltimore, Md. : 1950) (2016)
Expression of programmed death 1 (PD-1) on CD8 T cells promotes T cell exhaustion during chronic Ag exposure. During acute infections, PD-1 is transiently expressed and has the potential to modulate CD8 T cell memory formation. Conserved region C (CR-C), a promoter proximal cis-regulatory element that is critical to PD-1 expression in vitro, responds to NFATc1, FoxO1, and/or NF-κB signaling pathways. Here, a CR-C knockout mouse was established to determine its role on PD-1 expression and the corresponding effects on T cell function in vivo. Deletion of CR-C decreased PD-1 expression on CD4 T cells and Ag-specific CD8 T cells during acute and chronic lymphocytic choriomeningitis virus challenges, but did not affect the ability to clear an infection. Following acute lymphocytic choriomeningitis virus infection, memory CD8 T cells in the CR-C knockout mouse were formed in greater numbers, were more functional, and were more effective at responding to a melanoma tumor than wild-type memory cells. These data implicate a critical role for CR-C in governing PD-1 expression, and a subsequent role in guiding CD8 T cell differentiation. The data suggest the possibility that titrating PD-1 expression during CD8 T cell activation could have important ramifications in vaccine development and clinical care.
Keyphrases
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- transcription factor
- liver failure
- healthcare
- drug induced
- respiratory failure
- dna methylation
- immune response
- big data
- gene expression
- induced apoptosis
- chronic pain
- toll like receptor
- hepatitis b virus
- epithelial mesenchymal transition
- machine learning
- pi k akt
- acute respiratory distress syndrome
- health insurance
- extracorporeal membrane oxygenation