| First Author | Kalia V | Year | 2021 |
| Journal | Sci Transl Med | Volume | 13 |
| Issue | 615 | Pages | eaba6006 |
| PubMed ID | 34644150 | Mgi Jnum | J:325467 |
| Mgi Id | MGI:7279030 | Doi | 10.1126/scitranslmed.aba6006 |
| Citation | Kalia V, et al. (2021) Metabolic regulation by PD-1 signaling promotes long-lived quiescent CD8 T cell memory in mice. Sci Transl Med 13(615):eaba6006 |
| abstractText | Inhibitory signaling in dysfunctional CD8 T cells through the programmed cell death 1 (PD-1) axis is well established in chronic viral infections and cancers. PD-1 is also transiently induced to high concentrations during priming of acute infections and immunizations, yet its impact on the development of long-lived antigen-independent T cell memory remains unclear. In addition to its expected role in restraining clonal effector expansion, here, we show that PD-1 expression on antigen-specific CD8 T cells is required for the development of a durable CD8 T cell memory pool after antigen clearance. Loss of T cell-specific PD-1 signaling led to increased contraction and a defect in antigen-independent renewal of memory CD8 T cells in response to homeostatic cytokine signals, thus resulting in attrition of the memory pool over time. Whereas exhausted CD8 T cells regain function after PD-1 checkpoint blockade during chronic viral infection, the preexisting pool of resting functional bystander memory CD8 T cells established in response to a previously administered immunogen decreased. Metabolically, PD-1 signals were necessary for regulating the critical balance of mTOR-dependent anabolic glycolysis and fatty acid oxidation programs to meet the bioenergetic needs of quiescent CD8 T cell memory. These results define PD-1 as a key metabolic regulator of protective T cell immunity. Furthermore, these results have potential clinical implications for preexisting CD8 T cell memory during PD-1 checkpoint blockade therapy. |
