| First Author | Ciucci T | Year | 2019 |
| Journal | Immunity | Volume | 50 |
| Issue | 1 | Pages | 91-105.e4 |
| PubMed ID | 30638736 | Mgi Jnum | J:282390 |
| Mgi Id | MGI:6380786 | Doi | 10.1016/j.immuni.2018.12.019 |
| Citation | Ciucci T, et al. (2019) The Emergence and Functional Fitness of Memory CD4(+) T Cells Require the Transcription Factor Thpok. Immunity 50(1):91-105.e4 |
| abstractText | Memory CD4(+) T cells mediate long-term immunity, and their generation is a key objective of vaccination strategies. However, the transcriptional circuitry controlling the emergence of memory cells from early CD4(+) antigen-responders remains poorly understood. Here, using single-cell RNA-seq to study the transcriptome of virus-specific CD4(+) T cells, we identified a gene signature that distinguishes potential memory precursors from effector cells. We found that both that signature and the emergence of memory CD4(+) T cells required the transcription factor Thpok. We further demonstrated that Thpok cell-intrinsically protected memory cells from a dysfunctional, effector-like transcriptional program, similar to but distinct from the exhaustion pattern of cells responding to chronic infection. Mechanistically, Thpok- bound genes encoding the transcription factors Blimp1 and Runx3 and acted by antagonizing their expression. Thus, a Thpok-dependent circuitry promotes both memory CD4(+) T cells' differentiation and functional fitness, two previously unconnected critical attributes of adaptive immunity. |
