| First Author | Bally AP | Year | 2017 |
| Journal | J Immunol | Volume | 198 |
| Issue | 1 | Pages | 205-217 |
| PubMed ID | 27895178 | Mgi Jnum | J:240641 |
| Mgi Id | MGI:5888828 | Doi | 10.4049/jimmunol.1601464 |
| Citation | Bally AP, et al. (2017) Conserved Region C Functions To Regulate PD-1 Expression and Subsequent CD8 T Cell Memory. J Immunol 198(1):205-217 |
| abstractText | 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-kappaB 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. |
