| First Author | Snell LM | Year | 2018 |
| Journal | Immunity | Volume | 49 |
| Issue | 4 | Pages | 678-694.e5 |
| PubMed ID | 30314757 | Mgi Jnum | J:277996 |
| Mgi Id | MGI:6284414 | Doi | 10.1016/j.immuni.2018.08.002 |
| Citation | Snell LM, et al. (2018) CD8(+) T Cell Priming in Established Chronic Viral Infection Preferentially Directs Differentiation of Memory-like Cells for Sustained Immunity. Immunity 49(4):678-694.e5 |
| abstractText | CD8(+) T cell exhaustion impedes control of chronic viral infection; yet how new T cell responses are mounted during chronic infection is unclear. Unlike T cells primed at the onset of infection that rapidly differentiate into effectors and exhaust, we demonstrate that virus-specific CD8(+) T cells primed after establishment of chronic LCMV infection preferentially generate memory-like transcription factor TCF1(+) cells that were transcriptionally and proteomically distinct, less exhausted, and more responsive to immunotherapy. Mechanistically, adaptations of antigen-presenting cells and diminished T cell signaling intensity promoted differentiation of the memory-like subset at the expense of rapid effector cell differentiation, which was now highly dependent on IL-21-mediated CD4(+) T cell help for its functional generation. Chronic viral infection similarly redirected de novo differentiation of tumor-specific CD8(+) T cells, ultimately preventing cancer control. Thus, targeting these T cell stimulatory pathways could enable strategies to control chronic infection, tumors, and enhance immunotherapeutic efficacy. |
