Translational repression of 5' TOP mRNAs in chronically activated CD8+ T cells in vitro.

Pledger ES, Ambavaram N, Ferguson L, Cate JHD · 2026 · RNA biology · Atlas ID PLEDGER2026

What this study shows

Ribosome profiling of exhausted human CD8+ T cells reveals marked repression of 5'TOP mRNAs despite elevated mTOR activity, uncovering a layer of translational control that overrides or bypasses mTOR in T cell exhaustion.

Abstract

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T cell exhaustion is a dysfunctional state that arises during chronic infections and cancer, characterized by impaired effector functions and sustained expression of inhibitory receptors. We performed ribosome profiling and RNA sequencing on chronically activated human CD8+ T cells to globally assess translational control during a model of T cell exhaustion. Our analyses reveal a marked repression of 5' terminal oligopyrimidine (TOP) mRNAs during chronic activation. Unexpectedly, we demonstrate that this translational repression occurs despite evidence of elevated mTOR activity.

Read the full abstract on PubMed →

At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Human (CD8+ T cells in vitro)) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	Human (CD8+ T cells in vitro)
Journal	RNA biology
Year	2026
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1080/15476286.2026.2715355 · PMID 42558000 · Free full text (PMC13479822)

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Chronic T cell activation
Target	mTOR / 5'TOP mRNA translation
Model	Human
Effect	5'TOP mRNAs repressed despite elevated mTOR activity in exhausted CD8+ T cells

In the Atlas

Links in the pathway map

Supports mTORC1 activates 5'TOP mRNA

Cite this paper

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Pledger, E. S., Ambavaram, N., Ferguson, L., & Cate, J. H. D. (2026). Translational repression of 5' TOP mRNAs in chronically activated CD8+ T cells in vitro. RNA biology. https://doi.org/10.1080/15476286.2026.2715355

@article{PLEDGER2026,
  author       = {Pledger, E. S. and Ambavaram, N. and Ferguson, L. and Cate, J. H. D.},
  title        = {{Translational repression of 5' TOP mRNAs in chronically activated CD8+ T cells in vitro}},
  journal      = {RNA biology},
  year         = {2026},
  doi          = {10.1080/15476286.2026.2715355},
  note         = {PMID: 42558000},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record PLEDGER2026) [Data set]. https://mtor-atlas.org/study/PLEDGER2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_PLEDGER2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record PLEDGER2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/PLEDGER2026/},
  doi          = {10.5281/zenodo.22059963}
}

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