Single-cell RNA-seq reveals TOX as a key regulator of CD8+ T cell persistence in chronic infection.
Chen YaoHong-Wei SunNeal E LaceyYun JiE Ashley MosemanHan-Yu ShihElisabeth F HeustonMartha KirbyStacie AndersonJun ChengOmar KhanRobin HandonJulie ReilleyJessica FioravantiJinhui HuSelamawit GossaE John WherryLuca GattinoniDorian B McGavernJohn J O'SheaPamela L SchwartzbergTuoqi WuPublished in: Nature immunology (2019)
Progenitor-like CD8+ T cells mediate long-term immunity to chronic infection and cancer and respond potently to immune checkpoint blockade. These cells share transcriptional regulators with memory precursor cells, including T cell-specific transcription factor 1 (TCF1), but it is unclear whether they adopt distinct programs to adapt to the immunosuppressive environment. By comparing the single-cell transcriptomes and epigenetic profiles of CD8+ T cells responding to acute and chronic viral infections, we found that progenitor-like CD8+ T cells became distinct from memory precursor cells before the peak of the T cell response. We discovered a coexpression gene module containing Tox that exhibited higher transcriptional activity associated with more abundant active histone marks in progenitor-like cells than memory precursor cells. Moreover, thymocyte selection-associated high mobility group box protein TOX (TOX) promoted the persistence of antiviral CD8+ T cells and was required for the programming of progenitor-like CD8+ T cells. Thus, long-term CD8+ T cell immunity to chronic viral infection requires unique transcriptional and epigenetic programs associated with the transcription factor TOX.
Keyphrases
- transcription factor
- single cell
- rna seq
- induced apoptosis
- cell cycle arrest
- gene expression
- dna methylation
- public health
- working memory
- high throughput
- endoplasmic reticulum stress
- signaling pathway
- dna binding
- squamous cell carcinoma
- cell death
- oxidative stress
- genome wide
- liver failure
- extracorporeal membrane oxygenation
- pi k akt
- acute respiratory distress syndrome
- heat shock
- mechanical ventilation